Promethease Report

news The effectiveness of 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm birth is influenced by SNPs. Black women *rs471767 homozygous for the major allele treatment significantly reduced the rate of preterm birth. *rs578029 who had a least one copy of the major allele, treatment significantly reduced in preterm birth non-black women *a least one copy of the minor allele of rs503362 had a significant reduction with treatment *with at least one copy of the minor allele of rs666553 had a significant reduction in very preterm birth

news The effectiveness of 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm birth is influenced by SNPs. Black women *rs471767 homozygous for the major allele treatment significantly reduced the rate of preterm birth. *rs578029 who had a least one copy of the major allele, treatment significantly reduced in preterm birth non-black women *a least one copy of the minor allele of rs503362 had a significant reduction with treatment *with at least one copy of the minor allele of rs666553 had a significant reduction in very preterm birth

news The effectiveness of 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm birth is influenced by SNPs. Black women *rs471767 homozygous for the major allele treatment significantly reduced the rate of preterm birth. *rs578029 who had a least one copy of the major allele, treatment significantly reduced in preterm birth non-black women *a least one copy of the minor allele of rs503362 had a significant reduction with treatment *with at least one copy of the minor allele of rs666553 had a significant reduction in very preterm birth

news The effectiveness of 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm birth is influenced by SNPs. Black women *rs471767 homozygous for the major allele treatment significantly reduced the rate of preterm birth. *rs578029 who had a least one copy of the major allele, treatment significantly reduced in preterm birth non-black women *a least one copy of the minor allele of rs503362 had a significant reduction with treatment *with at least one copy of the minor allele of rs666553 had a significant reduction in very preterm birth

pharmgkb - defines *2A allele, which has a significantly higher chance of 5-fluorouracil toxicity [PharmGKB:In-Depth Heterozygosity for the A allele of this SNP is associated with mucositis and leukopenia drug toxicity in cancer patients treated with fluorouracil. Heterozygous males were more likely than heterozygous females to develop severe toxicity. In this study, no A/A homozygotes were observed.]

rs1127354 (Pro32Thr/P32T, 94C>A) is a SNP within the ITPA (Inosine triphosphate pyrophosphatase) gene. (note: rs1127354 supersedes rs41320251) abolishes IPTA activity in homozygous individuals and reduces the activity to 25% in heterozygous subjects, mercaptopurine metabolism (sig. higher methyl mercaptopurine nucleotides levels + higher probability of severe febrile neutropenia in A carriers treated with mercaptopurine) [PharmGKB:Curated This polymorphism in the ITPA gene had the highest correlation with the change in SLE disease activity index score (r = 0.354, P = 0.006).] [OMIM:INOSINE TRIPHOSPHATASE DEFICIENCY]

rs1800462, also known as A80P, is a rare SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP (in orientation to the dbSNP entry) is rs1800462(C), and it encodes the TPMT*2 allele. It may occur at a frequency of 1 in 200 alleles among Caucasians. wikipedia thiopurine drugs metabolized by TPMT include azathioprine, mercaptopurine, and thioguanine [PharmGKB:In-Depth The TPMT:238G>C SNP was cloned from a patient with severe mercaptopurine toxicity. It results in a non-synonymous protein change TPMT:Ala80Pro that has a 100-fold reduction in catalytic activity compared to w...

[PharmGKB:Curated Human lymphocyte cell lines homozygous for the A allele of this variant, common in Japanese populations, exhibit reduced surface membrane levels of ABCC4 protein and increased sensitivity to 6-mercaptopurine toxicity relative to cell lines homozygous for the G allele. The A-allele and G-allele cell lines have similar overall protein expression levels.]

rs1142345 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1142345(G), and when it is the only variant in the TPMT gene, it encodes the TPMT*3C allele. While still rare, it is more common in African-Americans (2.4% of all alleles) than in Caucasians. Note that if the same allele also carries the rs1800460(A) SNP, the allele is actually a TPMT*3A allele (OMIM). The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatment. spit...

rs1800460 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1800460(A), and when it is the only variation in the TPMT gene, it encodes the TPMT*3B allele. While still rare, it is more common in Caucasians (4.5% of all alleles) than in African-Americans (0.8%). Note that if the same allele also carries the rs1142345(G) SNP, the allele is actually a TPMT*3A allele (OMIM). The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatm...

rs1800584 is a rare SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The rs1800584(A) SNP defines the TPMT*4A allele (OMIM). wikipedia thiopurine drugs metabolized by TPMT include azathioprine, mercaptopurine, and thioguanine [PharmGKB:In-Depth This splicing variant results in very low TPMT activity and risk for hematologic toxicity as a result of treatment with thiopurines.]

rs2395029 is a SNP in the major histocompatibility complex (MHC) region, and several studies have shown that the rs2395029(G) allele is 99.9% predictive of the presence of an HLA-B*5701 allele. This HLA allele, in turn, has been associated with several conditions. A study of 51 cases of flucloxacillin drug-induced liver injury (DILI), an important cause of serious liver disease, along with a replication study of another 23 cases, found that the rs2395029(G) carriers were at highly increased risk (odds ratio 80, p=8.7x10(-33)). * see also: spittoon rs2395029(G;G) increases the odds of drug-induced liver injury in response to flucloxacillin by 45x This SNP is thought to be involved in determining the HIV viral load set point during the asymptomatic period of infection. This SNP is estimated ...

[PharmGKB:Curated Risk or phenotype-associated allele: allele 4. Phenotype: Tagging SNP for HLA-B*5701 (0.011 allele frequency). Study size: 45. Study population/ethnicity: Unrelated Han Chinese from Beijing, China. Significance metric(s): Type of association: GN]

A form of this snp, located upstream of the XPNPEP2 gene on the X chromosome, may cause susceptibility to skin swelling when taking medicines called ACE Inhibitors. Also known as -2399C/A in the literature; however in SNPedia, where the orientation of the corresponding dbSNP entry is recognized as primary, this is G/T. After noticing the association of this SNP with the phenotype, the authors genotyped 20 independent AE-ACEi cases and 60 unrelated, matching controls for this SNP. The T allele was present in 8 of the 20 AE patients; and by allele counting, the T allele was found at a frequency of 11.1% in the control population and 27.3% in their AE-ACEi cases. *See also OMIM 300145 [OMIM:?]

After taking Acetaminophen (Tylenol), rs1467558(A;G) individuals have higher alanine aminotransferase (ALT) levels, a sign of liver toxicity, than do (G;G) homozygotes. More studies are needed; there was only 1 (A;A) individual, and he didn't show elevated ALT levels; furthermore, the ALT increases were 'modest' anyway for (A;G) individuals compared to (G;G). see also: spittoon '''Note:''' the orientation of this SNP in SNPedia is as detailed in dbSNP, but in publications (including spittoon) the orientation is 'flipped', so what's (A;A) in dbSNP is (T;T) as discussed by spittoon.

rs10248420 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs10248420 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are kn...

[PharmGKB:Curated This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.]

rs11983225 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs11983225 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are kn...

rs4148739 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs4148739 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

[PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: The CYP2C19*17 allele was associated with significantly increased metabolism of imipramine. Study size: 178 Study population/ethnicity: Psychiatric patients aged 18-65 with a score of greater than or equal to 17 on the Hamilton Rating Scale for Depression. Significance metric(s): p = 0.035 Type of association: PK]

rs4148740 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs4148740 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs7787082 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs7787082 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs12720067 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs12720067 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are kn...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235015 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is near 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. rs2235015 has an r² value of >0.5 with this group. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported ...

rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235040 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235067 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235067 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. A study of 1,000+ breast cancer patients showed a 0.77x decreased risk of breast cancer for carriers of a CYP2C19*17 allele (CI: 0.65-0.93, p = 0.005). Analysis of a subgroup of such carriers who were using hormone therapy for ten years or longer showed an even stronger effect (odds ratio 0.57, CI: 0.39-0.83, p = 0....

[PharmGKB:Curated Protective allele: C; Phenotype: upon treatment with amlodipine, patients with C/C or C/T compared to a T/T genotype were twice as likely to reach a target mean arterial pressure (MAP) <107mmHG; study size: 145; study population: African-American men and women with early hypertensive nephrosclerosis ; significance value: hazards ratio 2.0; p-value 0.01]

rs527974 is a SNP in the calcium channel, voltage-dependent, L type, alpha 1D subunit CACNA1D gene. A study of 161 Japanese patients (85 men, 76 women) being treated for hypertension with L-type dCCBs (calcium channel blockers) concluded that rs527974(T) carriers responded better, as measured by lowered systolic and diastolic blood pressure readings.

rs3774426 is a SNP in the calcium channel, voltage-dependent, L type, alpha 1D subunit CACNA1D gene. A study of 161 Japanese patients (85 men, 76 women) being treated for hypertension with L-type dCCBs (calcium channel blockers) concluded that individuals with rs3774426(C;C) genotypes responded better, as measured by lowered systolic and diastolic blood pressure readings.

rs312481 is a SNP in the calcium channel, voltage-dependent, L type, alpha 1D subunit CACNA1D gene. A study of 161 Japanese patients (85 men, 76 women) being treated for hypertension with L-type dCCBs (calcium channel blockers) concluded that individuals with rs312481(C;C) genotypes responded better, as measured by lowered systolic and diastolic blood pressure readings.

rs5065, also known as T2238C, is a SNP in the atrial natriuretic precursor A NPPA gene. A large study has been conducted in which 42,418 hypertensive participants 55 or older were followed for several years while on one of four medications: a diuretic, a calcium antagonist, an angiotensin-converting enzyme inhibitor, or an alpha-blocker. The primary endpoint was either fatal heart disease or a heart attack. The blood pressure after six months of rs5065(G;G) patients (note: genotype is in dbSNP orientation, not as published) was lower if the patients were treated with diuretics compared to other medications, with smaller variation seen for (A;A) genotypes. The authors noted that none of the findings retained statistical significance after correction for multiple comparisons, but since the t...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs1045642, also known as C3435T, is a SNP located in the ABCB1 gene. It is often studied in conjunction with rs2032582. C3435T has been mentioned by: * A 'Silent' Polymorphism in the MDR1 Gene Changes Substrate Specificity (for example, to verapamil) * (R)-lansoprazole (Prevacid) concentrations are significantly increased in CYP2C19 extensive metabolizers with ABCB1 C3435T C allele. * In a Korean population, plasma concentrations of fexofenadine (Allegra) were 17% lower in 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects compared to 2677GG/3435CC subjects. * In contrast, in this study no association was observed between the C3435T polymorphism and fexofenadine plasma or urine concentrations in a German Caucasian population. * A meta-analysis including 9 case-control stud...

[PharmGKB:Curated This variant is found to be a risk marker for statin induced myalgia]

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

[PharmGKB:Curated This variant is found to be a risk marker for statin induced myalgia]

rs4149056, also known as 37041T>C or V174A, is a SNP in the SLCO1B1 gene, which encodes the 'organic anion transporting polypeptide 1B1' (OATP1B1) protein. This protein, found primarily in the liver, regulates the uptake of numerous drugs and natural compounds. The rs4149056(C) SNP defines the SLCO1B1*5 allele. The rs4149056(C) allele gives rise to an amino acid change (from valine to alanine at residue 174) which has reduced uptake/transport activity. Therefore, drugs metabolized by OATP1B1 tend to build up to higher circulating concentrations than they would otherwise.. The drugs known (or in some cases, thought) to be transported less well by the variant OATP1B1 protein encoded by the rs4149056(C) allele include: *Several cholesterol lowering statins, generally leading to reduced inh...

[PharmGKB:Curated Risk or phenotype-associated allele: 2012GT (671Gly/Val) genotype. Phenotype: Carriers the heterozygous 2012GT (671Gly/Val) genotype had lower serum HDL cholesterol than the GG (671Gly/Gly) genotype carriers (p = 0.015). Study size: 136. Study population/ethnicity: Hypercholesterolemic individuals, treated with atorvastatin (10mg/day/4 weeks), evaluated for CAD risk factors at the Institute Dante Pazzanese of Cardiology and the Hospital of the Sao Paulo University in Sao Paulo City, Brazil. Significance metric(s): p = 0.015. Type of association: GN; PD; FA]

rs5443, a SNP in the G-protein beta3 subunit (GNB3) gene that is more commonly known as the C825T variant, has been linked to a number of metabolic conditions including obesity, coronary artery disease, insulin resistance and therefore diabetes, left ventricular hypertrophy, and hypertension. It has also been linked to how well a patient responds to Viagra (sildenafil). Several studies have been unable to replicate one or more of the associations in at least some populations between this SNP and these conditions. The more notable studies include: *rs5443(T) allele carriers are 2-3 fold more likely to be obese in Caucasian, Chinese, and African American populations. *rs5443(T) carriers are clearly at higher risk for hypertension, but this review indicates that whether they are also at incre...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs1045642, also known as C3435T, is a SNP located in the ABCB1 gene. It is often studied in conjunction with rs2032582. C3435T has been mentioned by: * A 'Silent' Polymorphism in the MDR1 Gene Changes Substrate Specificity (for example, to verapamil) * (R)-lansoprazole (Prevacid) concentrations are significantly increased in CYP2C19 extensive metabolizers with ABCB1 C3435T C allele. * In a Korean population, plasma concentrations of fexofenadine (Allegra) were 17% lower in 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects compared to 2677GG/3435CC subjects. * In contrast, in this study no association was observed between the C3435T polymorphism and fexofenadine plasma or urine concentrations in a German Caucasian population. * A meta-analysis including 9 case-control stud...

In Caucasian non-Hispanics, the rs1360780(T) allele is associated with increased risk for depression, with an odds ratio of 1.39 (CI: 1.14-1.70, p=0.046). This same SNP, which is in the FKBP5 gene, may influence how patients respond to antidepressants including citalopram. rs1360780(T;T) homozgyotes tend to report more depressive episodes, but they also respond better to treatment with antidepressants. rs9296158 rs3800373 rs1360780 rs9470080 linked with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. [PharmGKB:Curated This variant is associated with higher chance of response to anti-depressant drugs.] [OMIM:FK506-BINDING PROTEIN 5; FKBP5]

Trajectories of change in depression severity during treatment with antidepressants. Pharmacogenomics of antidepressant drugs.

rs10248420 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs10248420 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are kn...

rs11983225 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs11983225 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are kn...

rs4148739 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs4148739 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs4148740 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs4148740 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs7997012, located in an intron of the HTR2A gene, was found to be associated with a somewhat increased rate of successful response to treatment of depression with the drug citalopram. From this article : 'HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram. Participants who were homozygous for the A allele had an 18% reduction in absolute risk of having no response to treatment, compared with those homozygous for the other allele.' * See also Anxiety Blog posting [PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: Patients with the 5-HTR2A intron 2 (rs7997012) AA genotype suffered from more pronounced side effects compared to carriers of the GA or GG genotype. Study size: 124. Study population/ethnicity: Caucasian; Patients with psychiatric diso...

rs908867 is a SNP near the brain-derived neurotrophic factor BDNF gene. In a study of , the rs908867 was associated with antidepressant response, with heterozygote carriers showing a better response than homozygotes. However, a critique of this study was published , indicating that this finding should be viewed as preliminary until more research is conducted for several reasons, to wit, 'First, the study included not only major depression but also bipolar disorder patients; second, various antidepressants were used in this study, which could affect patients' responses; third, the frequency of the haplotype associated with treatment response is rare; and fourth, previous studies of the effects of single BDNF polymorphisms on antidepressant action have reported conflicting findings.'

rs7787082 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs7787082 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs12720067 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs12720067 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are kn...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235015 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is near 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. rs2235015 has an r² value of >0.5 with this group. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported ...

rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235040 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235067 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235067 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

The 'A2' allele of the platelet specific alloantigen system is encoded by rs5918(C), and it has been implicated as increasing the risk of myocardial infarctions, heart disease, and resistance to blood-thinning benefits of aspirin. On it's own, the A2 allele is implicated especially in early onset heart disease ; in combination with the 4G allele of the PAI1 gene, rs1799889, the increased risk of myocardial infarction in a Finnish study population was 4 fold higher (odds ratio = 4.5, p=0.001), particularly in males (odds ratio = 6.4, p=0.0005) . A2 allele carriers also appear to be relatively resistant to the anti-thrombotic (i.e. anti-clotting) actions normally associated with aspirin use. A protective effect of rs5918 has also been observed for the development of Non-Hodgkin Lymphoma, bot...

[PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: A-444C was associated with aspirin-induced urticaria (AIU). The C allele was more frequent in patients with the cutaneous pattern of AIU and in patients with low skin reactivity to histamine. Study size: 110 patients with AIU and 165 nonallergic controls .]

[PharmGKB:Curated This variant is associated with enhanced agonist-induced platelet aggragation and response to aspirin in both whites and african americans. The C allele was associated with increased aggregation of native platelets to collagen, epinephrine. The C allele was also associated with reduced platelet responsiveness to aspirin. (N=1486)]

rs1799853 is a SNP in the CYP2C9 gene. The rs1799853(T) allele encodes a variant amino acid, cysteine, which has been linked to poor metabolism of warfarin and thus sensitivity . The common nomenclature for this polymorphism is CYP2C9*2 (Cys amino acid, T allele; the SNP is also known as C430T or Cys144Arg). The effect of CYP2C9 variants on drug metabolism should not be predicted without also considering CYP2C9*3, defined as the common loss of function variant rs1057910(C) (NM_000771:c.430C>T, NP_000762:p.144R>C) [http://www.pharmgkb.org/search/annotatedGene/cyp2c9/. Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of nonsteroidal anti-inflammatory drugs (NSAIDs) that are CYP2C8 or CYP2C9 substrates, such as aceclofena...

rs10935838, rs2046934, rs5853517, and rs6809699 venous thromboembolism lower risk of incident DVT/PE as compared to the reference haplotype H1 (odds ratio=0.50, 95% CI=0.27-0.93, p=0.028) [PharmGKB:Curated This SNP was used to tag the H2 haplotype to show association with peripherial arterial disease and coronary artery disease.]

SNP rs1057910(A), located in the cytochrome p450 CYP2C9 gene, most commonly encodes the amino acid isoleucine at position 359, and the resulting allele is also known as CYP2C9*1. rs1057910(C) encodes a leucine at this same position, and the resulting allele is called CYP2C9*3. This SNP is also known as Ile359Leu or A1075C. The effect of CYP2C9 variants on drug metabolism should not be predicted without also considering CYP2C9*2, defined as the common loss of function variant rs1799853(T) (NM_000771:c.430C>T, NP_000762:p.144R>C) Studies of the effects of these alleles include: * rs1057910(C;C)] genotypes may clear drugs like celecoxib (trade name Celebrex) twice as slowly as rs1057910(A;A) genotypes; the rs1057910(A;C) genotypes are in-between clearance rates. Lower clearance rates wi...

rs9332131, also known as 818delA, 10601delA or 273Frame shift, is a SNP in the CYP2C9 gene. The rs9332131(-) allele defines the CYP2C9*6 variant, which is inactive. [PharmGKB:Curated Phenotype: In African Americans patients, weekly warfarin dose requirements were lower in those with the CYP2C9*8 allele (34 (30-47) mg; P = 0.023) and the CYP2C9 *2, *3, *5, *6, or *11 allele (33(28-40 mg); P < 0.001) as compared with those with the CYP2C9*1/*1 genotype (43 (35-56) mg). Adding the *5,*6,*8 and *11 alleles to a model containing the *2 and *3 alleles plus the VKORC1 -1639 G>A allele (along with clinical variables) explained 36% vs. 30% of the variability in dose requirements. Study size: 226 . Study population/ethnicity: African-American . Type of association: PD;GN;CO]

rs3842787, also known as 50C>T, is a SNP in the signal peptide region of the cyclooxygenase-1 PTGS1 gene. A study of 696 European patients undergoing elective diagnostic coronary angiographies (CAGs) because of suspected or proven stable coronary artery disease found that 23 experienced bleeding, perhaps the most common complication of this type of invasive coronary procedure. After controlling for various variables (especially gender), two co-inherited SNPs, rs10306114 and rs3842787, were found to be associated with higher risk for bleeding in otherwise low risk patients who (i) did undergo percutaneous coronary intervention and (ii) did not take clopidogrel. Having the less common haplotype (rs10306114(G) and/or rs3842787(T)) increases the bleeding risk upon CAG ~12 fold (p = 0.012). ...

rs28371685, also known as 1003C>T, 42542C>T or R335W is a SNP in the CYP2C9 gene. The rs28371685(T) allele defines the CYP2C9*11 variant, which has decreased activity. According to a 23andMe discussion This is one of the SNPs which were re-analyzed April 2009. Customers with older data may wish to redownload. SNPs effected rs4420638, rs34276300, rs3091244, rs34601266, rs2033003, rs7900194, rs9332239, rs28371685, rs1229984, and rs28399504. [PharmGKB:Curated Phenotype: In African Americans patients, weekly warfarin dose requirements were lower in those with the CYP2C9*8 allele (34 (30-47) mg; P = 0.023) and the CYP2C9 *2, *3, *5, *6, or *11 allele (33(28-40 mg); P < 0.001) as compared with those with the CYP2C9*1/*1 genotype (43 (35-56) mg). Adding the *5,*6,*8 and *11 alleles to a...

rs3798220, also known as I4399M or Ile4399Met, is a SNP in the apolipoprotein(A) LPA gene that has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and increased cardiovascular risk, and in particular, coronary artery disease. In one study, 25,131 initially healthy Caucasian participants in the Women's Health Study were followed for ~10 years. rs3798220(C) allele carriers (3.7%) in the placebo (i.e. not receiving aspirin) group had a 2x higher risk of major cardiovascular events than non-carriers (age-adjusted hazard ratio (HR) of 2.21, CI: 1.39-3.52). Among rs3798220(C) carriers, the risk was reduced more than twofold by aspirin: for aspirin compared with placebo the age-adjusted HR was 0.44 (CI: 0.20-0.94). The risk was not significantly reduced among non-carrie...

rs28371686, also known as 1080C>G, 42619C>G or D360E, is a SNP in the CYP2C9 gene. The rs28371686(G) allele defines the CYP2C9*5 variant, which appears to have decreased activity. [PharmGKB:Curated Phenotype: In African Americans patients, weekly warfarin dose requirements were lower in those with the CYP2C9*8 allele (34 (30-47) mg; P = 0.023) and the CYP2C9 *2, *3, *5, *6, or *11 allele (33(28-40 mg); P < 0.001) as compared with those with the CYP2C9*1/*1 genotype (43 (35-56) mg). Adding the *5,*6,*8 and *11 alleles to a model containing the *2 and *3 alleles plus the VKORC1 -1639 G>A allele (along with clinical variables) explained 36% vs. 30% of the variability in dose requirements. Study size: 226 . Study population/ethnicity: African-American . Type of association: PD;GN;...

Far away from the other TPMT snps, this one comes from OMIM. dbSNP's geneview suggests that (G) should be normal, and (A) should be variant, but based this on 'no gene model'. 23andMe doesn't seem to actually be reporting this snp any longer. [OMIM:THIOPURINE S-METHYLTRANSFERASE DEFICIENCY]

[PharmGKB:Curated A study in a cohort of 192 patients receiving azathioprine for inflammatory bowel disease found that this SNP in the AOX1 gene predicted lack of azathioprine response (p=0.035, OR 2.54, 95%CI 1.06-6.13).]

rs1127354 (Pro32Thr/P32T, 94C>A) is a SNP within the ITPA (Inosine triphosphate pyrophosphatase) gene. (note: rs1127354 supersedes rs41320251) abolishes IPTA activity in homozygous individuals and reduces the activity to 25% in heterozygous subjects, mercaptopurine metabolism (sig. higher methyl mercaptopurine nucleotides levels + higher probability of severe febrile neutropenia in A carriers treated with mercaptopurine) [PharmGKB:Curated This polymorphism in the ITPA gene had the highest correlation with the change in SLE disease activity index score (r = 0.354, P = 0.006).] [OMIM:INOSINE TRIPHOSPHATASE DEFICIENCY]

rs1800462, also known as A80P, is a rare SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP (in orientation to the dbSNP entry) is rs1800462(C), and it encodes the TPMT*2 allele. It may occur at a frequency of 1 in 200 alleles among Caucasians. wikipedia thiopurine drugs metabolized by TPMT include azathioprine, mercaptopurine, and thioguanine [PharmGKB:In-Depth The TPMT:238G>C SNP was cloned from a patient with severe mercaptopurine toxicity. It results in a non-synonymous protein change TPMT:Ala80Pro that has a 100-fold reduction in catalytic activity compared to w...

rs1142345 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1142345(G), and when it is the only variant in the TPMT gene, it encodes the TPMT*3C allele. While still rare, it is more common in African-Americans (2.4% of all alleles) than in Caucasians. Note that if the same allele also carries the rs1800460(A) SNP, the allele is actually a TPMT*3A allele (OMIM). The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatment. spit...

rs1800460 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1800460(A), and when it is the only variation in the TPMT gene, it encodes the TPMT*3B allele. While still rare, it is more common in Caucasians (4.5% of all alleles) than in African-Americans (0.8%). Note that if the same allele also carries the rs1142345(G) SNP, the allele is actually a TPMT*3A allele (OMIM). The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatm...

rs1800584 is a rare SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The rs1800584(A) SNP defines the TPMT*4A allele (OMIM). wikipedia thiopurine drugs metabolized by TPMT include azathioprine, mercaptopurine, and thioguanine [PharmGKB:In-Depth This splicing variant results in very low TPMT activity and risk for hematologic toxicity as a result of treatment with thiopurines.]

[PharmGKB:Non-Curated Reduced TEA and betaine uptake in transfected cells]

[PharmGKB:Non-Curated Reduced TEA and betaine uptake in transfected cells]

[PharmGKB:Non-Curated Reduced TEA and betaine uptake in transfected cells]

Testicular cancer patients may be treated with bleomycin, a cytotoxic drug that is essential component of chemotherapy regimens for this cancer, officially known as disseminated testicular germ-cell cancer (TC). rs1050565 is a SNP in the BLMH gene. This gene encodes a protein that can inactivate bleomycin. Based on a study of 300 TC patients treated with bleomycin, a testicular cancer patient with a rs1050565(G;G) genotype has an odds ratio of 4.97 (CI: 2.17 - 11.39) for TC-related death compared to (A;G) or (A;A) genotypes. The rs1050565(G;G) genotype also shows a higher prevalence of early relapses. [PharmGKB:Curated Testicular germ cell cancer patients carrying the homozygous G/G allele of this variant showed reduced survival and higher prevalence of early relapses after treatment with...

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized f...

rs1042713, also known as Arg16, G16R, and 16Arg>Gly, is a SNP in the adrenergic, beta-2-, surface receptor ADRB2 gene. The rs1042713(G) allele encodes the G/glycine form that is the more common one in most populations, while rs1042713(A) encodes the R/arginine residue at this position of the ADRB2 protein. A study of 1,182 young Scottish asthma patients (age, 3-22 years) concluded that rs1042713(A) alleles are significantly associated with 'exacerbations' of their condition, regardless of treatment regimens (odds ratio 1.30, CI: 1.09-1.55, p=0.003). This didn't hold true for patients using inhalers less than once per day; and it was particularly true for those receiving daily inhaled long- or short-acting beta(2)-agonist treatment (OR, 1.64, CI: 1.22-2.20, p=.001). This may therefore in...

[PharmGKB:Curated This variant is associated with severe exacerbations with asthma in both white and african american childen. This variant also leads to decreased FEER2 expression and may be used to predict treatment outcome in asthma.]

associated with bronchodilator response among a sample of 209 children and their parents participating in the Childhood Asthma Management Program, the minor allele was associated with lower BDR compared to the homozygous major allele [PharmGKB:Curated This variant is associated with acute response to inhaled ? agonists in both childhood and adult asthmatic patients.]

This SNP encodes a variation in the 33rd amino acid of the protein encoded by the TBX21 gene. Although 95% or so of all Caucasians carry two copies of the rs2240017(G) allele, as oriented in dbSNP orientation, and are thus rs2240017(G;G) homozygotes, a few individuals are rs2240017(C;G) heterozygotes. These heterozgotes are reported to improve better over time in response to corticosteroid treatment for asthma than the rs2240017(G;G) homozygotes. So far, studies have not linked, however, this SNP to any change in the overall risk of asthma itself. Although the effect observed was strong, in that treating rs2240017(C;G) heterozygotes ultimately (over 4 years) yields average airway responsiveness in the normal range (i.e. in the same range as for nonasthmatics), the authors point out that th...

part of a three marker haplotype rs737865-rs4680-rs165599 COMT haplotypes at rs737865 and rs165599 may predict a favorable outcome for bupropion treatment for smoking cessation. We have typed the IVS 1 rs737865 and 3' rs615599 sites and also included a novel IVS 1 indel polymorphism. We report that the schizophrenia-associated haplotype is significantly heterogeneous in populations worldwide. may affect non-Hodgkin lymphoma, anxiety-related personality traits Also mentioned in these PMIDs * * * * * * [PharmGKB:Curated This variant may predict a favorable outcome for bupropion treatment for smoking cessation] [OMIM:CATECHOL-O-METHYLTRANSFERASE; COMT]

rs1799732 is a SNP in the D2 dopamine receptor gene DRD2 gene. Although dbSNP indicates the alleles as (C) or (-) (i.e. a deletion), investigators report the alleles as (C) or (T). In a study of individuals in the Polyp Prevention Trial with any, multiple (>/=2) or advanced colorectal adenoma recurrence after 4 years, compared to those without adenoma recurrence, rs1799732(C;T) individuals were significantly associated with all adenoma recurrence (odds ratio 1.30, CI: 1.01-1.69). The authors speculate this increased risk of adenoma recurrence (and an association with colorectal cancer) may be related to SNP-associated differences in alcohol and fat intake. spittoon Alcoholism related *rs1799971(A;A) severe alcoholism 2x *rs1799732(I;I) severe alcoholism 1.85x [PharmGKB:Curated Risk or ...

rs1800497, a SNP also known as the TaqIA (or Taq1A) polymorphism of the dopamine D2 receptor DRD2 gene (even though it is actually located over 10,000bp downstream of the gene), gives rise to the DRD2*A1 allele. This allele (rs1800497(T)) is associated with a reduced number of dopamine binding sites in the brain , and has been postulated to play a role in alcoholism, smoking, and certain neuropsychiatric disorders. The reduced number of dopamine binding sites may play a role in nicotine addiction by causing an 'understimulated' state that can be relieved by smoking (and/or use of other drugs). A wide variety of reports have been published over more than ten years either linking rs1800497 to aspects of nicotine use and smoking cessation success, or finding no such association. A meta-analys...

anxiety-related personality traits, ADHD, schizophrenia part of a three marker haplotype rs737865-rs4680-rs165599 epistasis between SNPs in COMT (rs2097603, Val158Met (rs4680), rs165599) and polymorphisms in other schizophrenia susceptibility genes popular in pubmed is associated with bipolar disorder and influences prefrontal aspects of verbal memory in bipolar patients and healthy controls. [PharmGKB:Curated In a study of 78 African American and 65 white patients diagnosed with schizophrenia or schizoaffective disorder, this SNP in the COMT gene was found to have significant associations with response to risperidone over 2-12 weeks in both African-American and white patients.] [OMIM:CATECHOL-O-METHYLTRANSFERASE; COMT]

rs2279343, also known as Lys262Arg, is a SNP within the CYP2B6 gene. variants including the Arg allele include CYP2B6*4, CYP2B6*6, and CYP2B6*7 [PharmGKB:In-Depth Risk or phenotype-associated allele: G. Phenotype: CYP2B6*4 genotype in the transplant recipient was associated with oral mucositis. Study size:107 . Study population/ethnicity: Donors and patients with leukemia after HLA-identical hematopoietic stem cell transplantation, France. Significance metric(s): p = 0.0067. Type of association: TOX]

[PharmGKB:In-Depth Risk or phenotype-associated allele: TC. Phenotype: This variant is statistically correlated with the mean of maximum transaminase values (ALT) in patients from Mozambique, with ALT mean value of 91.68 U/l for TT, and 221.45 U/l for TC genotypes (p < 0.001). Study size: 156. Study population/ethnicity: HIV infected patients from Mozambique. Significance metric(s): p< 0.001. Type of association: GN; CO]

rs3211371, also known as 1459C>T, is a SNP encoding the CYP2B6*5 allele of the CYP2B6 gene. [PharmGKB:Curated CYP2B6:1459C>T has been reported to reduce CYP2B6 protein expression in human liver and brain. Impact on drug response is somewhat contradictory, see VIP annotation for details.]

[PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: CYP2B6 mRNA expression and bupropion hydroxylase activity were approximately 2-fold higher in livers genotyped -82TC as in those genotyped -82TT. Study size: 85 (expression); 77 (activity). Study population/ethnicity: Non-tumorous liver samples from White individuals, Germany. Significance metric(s): p = 0.007 (expression); p = 0.042 (activity). Type of association: FA; PD]

Variation at this SNP, located in the ADRB1 gene, may encode either the amino acid serine or glycine at amino acid position 49 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Ser49Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801253, which encodes an amino acid variant at position 389 of the same (ADRB1) protein. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized for patients with the corresponding genotypes as follows : *rs1801252(A...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized f...

rs34815109 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene. This gene encodes a protein that modifies hepatic bilirubin in order to allow it to be excreted. SNPs that reduce the activity of the UGT1A1 gene therefore tend to increase serum bilirubin levels. The rs34815109(TA) allele represents the insertion variant, which actually adds a seventh (TA) pair to what is already a string of six (TA) pairs; this reduces the activity to 30% of normal, and is thus the risk allele. The risk allele is commonly referred to as the UGT1A1*28 allele, and it is homozygous in ~10% of the US population. Risks associated with the rs34815109(TA) allele are almost always associated with the homozygous (TA;TA) genotype, with smaller (or no) effects...

rs34983651 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene; the primary entry in SNPedia for this set of SNPs is at rs34815109. The other two SNPs (besides rs34815109) that also describe the same polymorphism are: * rs35600288 * rs5839491

rs35600288 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene; the primary entry in SNPedia for this set of SNPs is at rs34815109. The other two SNPs (besides rs34815109) that also describe the same polymorphism are: * rs34983651 * rs5839491

rs5839491 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene; the primary entry in SNPedia for this set of SNPs is at rs34815109. The other two SNPs (besides rs34815109) that also describe the same polymorphism are: * rs35600288 * rs34983651

This SNP in the tumor necrosis factor-alpha gene, rs1800629, is also known as the TNF-308 SNP. Occasionally the rs1800629(A) allele is referred to as 308.2 or TNF2, with the more common (G) allele being 308.1 or TNF1. The (A) allele is associated with higher levels of TNF expression. This SNP has been linked to a wide variety of conditions: * Allograft rejection ** Among 72 Polish patients receiving a kidney transplant, the risk of acute kidney allograft rejection was 2.5x higher among rs1800629(A) carriers compared to (G;G) homozygotes (CI: 1.19- 5.37, p<.05). * Asthma ** A meta-analysis of ~2,500 patients combined indicated that the rs1800629(A) allele was associated with a 1.46x increased risk for asthma. ** In a study of ~600 Mexican families and their asthmatic children, rs1800629(...

rs2234922, also known as His139Arg, is a SNP in the microsomal epoxide hydrolase EPHX1 gene. [PharmGKB:Curated Risk or phenotype-associated allele: G. Phenotype: In a logistic regression model adjusted for history of phenytoin use during the first trimester and maternal epilepsy, the maternal EPHX1 139 R (rs2234922A/G) allele was associated with craniofacial abnormalities in the child. Study size: 157 pregnancies. Study population/ethnicity: phenytoin use during the first trimester and maternal epilepsy. metric(s): per rare allele OR: 2.33, 95% CI: 1.09-5.00, P=0.03. Type of association: GN.] [OMIM:EPOXIDE HYDROLASE POLYMORPHISM]

Genetic predictors of the maximum doses patients receive during anti-epileptic drugs carbamazepine and phenytoin Possible commercial test [PharmGKB:Curated This SNP is associated with required dose levels of antieptilectic drugs. It affects alternative splicing and hence the proportions of neonate and adult alternative transcripts of SCN1A in adult brain tissue. The effect of the polymorphism appears to be modified by Nova2 expression levels.] [OMIM:SODIUM CHANNEL, NEURONAL TYPE I, ALPHA SUBUNIT; SCN1A]

[PharmGKB:Curated Risk or phenotype-associated allele: G allele. Phenotype: Carbamazepine (CBZ)-induced hypersensitivity syndrome (HSS). Study size: 157. Study population/ethnicity: 13 CBZ-induced HSS cases and 144 CBZ-tolerant controls of Chinese descent. Significance metric(s): p = 0.002381, OR = 3.86. Type of association: GN; PD; TOX; ADR.]

A Danish case-control study comprising 373 Crohn's disease and 541 ulcerative colitis patients (and 796 healthy controls) concluded that carriers of the homozygous COX-2 and MDR1 intron 3 variant (rs3789243) had a relatively high risk of CD, odds ratio (95% CI) (OR (95% CI))=2.86 ((1.34-5.88) p=0.006) and 1.39 ((0.99-1.92) p=0.054), respectively, and for UC of 2.63 ((1.33-5.26) p=0.005) and 1.28 ((0.96-1.51) p=0.093), respectively, assuming complete dominance. [PharmGKB:Curated This variant maybe associated with drug resistance in chinese epilepsy patients. Sample size: 464 chinese epilepsy patients (270 drug responsive, 194 drug resistant).] [OMIM:ATP-BINDING CASSETTE, SUBFAMILY B, MEMBER 1; ABCB1]

[PharmGKB:Curated Risk or phenotype-associated allele: A allele. Phenotype: The A allele rs2894342, which lies in the promoter of MLN, is associated with carbamazepine (CBZ)-induced maculopapular exanthema (MPE)/ hypersensitivity syndrome (HSS). Study size: 175. Study population/ethnicity: 31 CBZ-induced MPE/HSS cases and 144 CBZ-tolerant controls of Chinese descent. Significance metric(s): p = 0.00342, OR = 2.88. Type of association: GN; PD; TOX; ADR.]

[PharmGKB:Curated Risk or phenotype-associated allele: G allele (602Glu). Phenotype: Carbamazepine (CBZ)-induced hypersensitivity syndrome (HSS). Study size: 157. Study population/ethnicity: 13 CBZ-induced HSS cases and 144 CBZ-tolerant controls of Chinese descent. Significance metric(s): p = 0.001173, OR = 7.31. Type of association: GN; PD; TOX; ADR.] [OMIM:HEAT-SHOCK 70-KD PROTEIN-LIKE 1; HSPA1L]

rs1051740, also known as Tyr113His, is a SNP in the microsomal epoxide hydrolase EPHX1 gene. severe hypersensitivity syndrome, triggered by carbamazepine in the presence of a concomitant active human herpes virus (HHV) 6 and 7 infection with the allele HLA-A*3101 and rs1051740(C;C) [PharmGKB:Curated Risk or phenotype-associated allele: T. Phenotype: In a logistic regression model adjusted for history of phenytoin use during the first trimester and maternal epilepsy, the maternal EPHX1 113 H (rs1051740 T/C) allele was associated with craniofacial abnormalities in the child. Study size: 157 pregnancies. Study population/ethnicity: phenytoin use during the first trimester and maternal epilepsy. metric(s): per rare allele OR: 2.43, 95% confidence interval (CI): 1.16-5.10, P=0.02. Type of asso...

[PharmGKB:Curated Risk or phenotype-associated allele: C allele. Phenotype: Carbamazepine (CBZ)-induced maculopapular exanthema (MPE)/ hypersensitivity syndrome (HSS). Study size: 175. Study population/ethnicity: 31 CBZ-induced MPE/HSS cases and 144 CBZ-tolerant controls of Chinese descent. Significance metric(s): p = 0.001696, OR = 2.51. Type of association: GN; PD; TOX; ADR.]

[PharmGKB:Curated Risk or phenotype-associated allele: C allele. Phenotype: Carbamazepine (CBZ)-induced maculopapular exanthema (MPE). Study size: 162. Study population/ethnicity: 18 CBZ-induced MPE cases and 144 CBZ-tolerant controls of Chinese descent. Significance metric(s): p = 0.007597, OR = 3.19. Type of association: GN; PD; TOX; ADR.]

[PharmGKB:Curated The T allele of this SNP is part of a haplotype that has been associated with protection from hypersensitivity to carbamazepine.]

[PharmGKB:Curated Risk or phenotype-associated allele: T allele. Phenotype: The T allele of rs3130690 (36 kb telomeric to HLA-B), which is strongly associated with the HLA-B*1502 allele, shows strong association with carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/Toxic Epidermal Necrolysis (TEN, Lyell's syndrome) (OR = 254.6 for TT/TG genotype versus GG genotype; T allele only: p = 4.66x10(-42), Pc = 1.29x10(-39), OR = 45.65). Also, an extended haplotype with rs3130690 T, HLA-B*1502, and other alleles of major histocompatibility complex genes (A*1101-Cw*0801-HLABC-CA*119-rs3130690T-B*1502-MICA*019-DRB1*1202) was in strong association with CBZ-induced SJS/TEN. Study size: 204. Study population/ethnicity: 60 CBZ-induced SJS/TEN cases and 144 CBZ-tolerant controls of Chinese desce...

[PharmGKB:Curated Risk or phenotype-associated allele: C allele. Phenotype: The C allele of rs750332 shows strong association with carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/Toxic Epidermal Necrolysis (TEN, Lyell's syndrome). Study size: 204. Study population/ethnicity: 60 CBZ-induced SJS/TEN cases and 144 CBZ-tolerant controls of Chinese descent. Significance metric(s): p = 3.04x10(-14), Pc = 8.45x10(-12), OR = 6.41. Type of association: GN; PD; TOX; ADR.]

[PharmGKB:Curated Risk or phenotype-associated allele: G allele. Phenotype: The G allele of rs1264511 shows strong association with carbamazepine (CBZ)-induced maculopapular exanthema (MPE)/ hypersensitivity syndrome (HSS). Study size: 175. Study population/ethnicity: 31 CBZ-induced MPE/HSS cases and 144 CBZ-tolerant controls of Chinese descent. Significance metric(s): p = 0.001685, OR = 3.13. Type of association: GN; PD; TOX; ADR.]

[PharmGKB:Curated Risk or phenotype-associated allele: C allele. Phenotype: The C allele of rs2848716 shows strong association with carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/Toxic Epidermal Necrolysis (TEN, Lyell's syndrome). Study size: 204. Study population/ethnicity: 60 CBZ-induced SJS/TEN cases and 144 CBZ-tolerant controls of Chinese descent. Significance metric(s): p = 7.58x10(-17), Pc = 2.10x10(-14), OR = 6.86. Type of association: GN; PD; TOX; ADR.]

Helps to identify HLA-B*1502 [PharmGKB:Curated Risk or phenotype-associated allele: allele 2. Phenotype: Combined alleles of rs3909184 (2) and rs2844682 (4) are tagging SNPs for HLA-B*1502 (0.011 allele frequency). Study size: 45. Study population/ethnicity: Unrelated Han Chinese from Beijing, China. Significance metric(s): Type of association: GN]

rs2273697, also known as c1249G>A or p.V471I, is a nonsynonymous polymorphism in the ABCC2 gene. From an initial case-control study of 146 patients with epilepsy, followed by replication (p=0.001) in another 279 patients, the rs2273697(A) allele was associated with neurological adverse drug reactions from taking carbamazepine. Functional studies showed that this SNP selectively reduced carbamazepine transport across the cell membrane. [PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: This SNP showed a strong association with the neurological adverse drug reaction caused (ADR) by carbamazepine (P=0.005). The study results indicate that the c.1249A variant is an independent risk factor of carbamazepine CNS ADR. Study size: 146 patients with epilepsy who had been prescr...

rs2227956 in HSP70-hom, resulted in a significant association with noise-induced hearing loss [PharmGKB:Curated The C allele of this SNP is part of a haplotype that has been associated with protection from hypersensitivity to carbamazepine.] [OMIM:?]

Helps to identify HLA-B*1502 [PharmGKB:Curated Risk or phenotype-associated allele: allele 4. Phenotype: Combined alleles of rs3909184 (2) and rs2844682 (4) are tagging SNPs for HLA-B*1502 (0.011 allele frequency). Study size: 45. Study population/ethnicity: Unrelated Han Chinese from Beijing, China. Significance metric(s): Type of association: GN]

rs2304016 (IVS7-32A>G) is a SNP within the SCN2A (sodium channel, voltage-gated, type II, alpha subunit). among 471 Chinese epilepsy patients (of which 272 were drug responsive and 199 drug resistant), A-allele carriers associated with resistance to anti-epileptic drugs (OR 2.1, 95% CI 1.2-3.7, p=0.007), haplotypes containing A-alleles were also associated w/ drug resistance [PharmGKB:Curated The A allele of this SNP was associated with resistance to sodium channel-blocking anti-epileptic drugs in a Chinese patient population.]

rs12721627, also known as 554C>G, 15603C>G or T185S, is a SNP in the CYP3A4 gene. The rs12721627(G) allele defines the CYP3A4*16 variant. [PharmGKB:Curated in vitro study; PK: variant shows substrate altered kinetics compared to wild type]

Several susceptibilities have been linked to rs1042714, a SNP in the ADRB2 gene that is also known as the Q27E SNP. The rs1042714(C) allele encodes the glutamine (Gln; 'Q'), and the rs1042714(G) allele encodes the glutamic acid (Glu; 'E'). A study of 304 patients found that the Glu27 allele led to increased risk for idiopathic venous thromboembolism; the reported odds ratio was 1.40 (CI: 1.09-1.79, p=0.006) for carriers of at least one risk allele. A study of 334 families with at least one child with autism found that increased risk associated with the rs1042714(G;G) homozygous genotype; the odds ratio reported was between 1.33-1.60 (CI: 1.07-2.58). The risk was approximately doubled among mothers who had clinical markers for pregnancy related stress. In a study of 342 patients with type-2...

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized f...

rs1801274 is a SNP in the Fc fragment of IgG, low affinity IIa, receptor (CD32) FCGR2A gene. rs1801274(C) encodes the arginine (R) allele, with the (T) allele encoding the variant histidine (H). The (H) isoform is considered high-binding to IgG2 and IgG3, while the (R) isoform is considered low-binding. This SNP is known in the literature by many names, including A519C and R131H. What's the importance of this? FcgR isoforms expressed on immune system cells have been linked to the pathogenic consequences triggered by autoantibodies or immune complexes in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as well as to the efficacy of some immunotherapeutic treatments such as rituximab. Many studies have been published about this FCGR2A SNP, roughly...

rs5065, also known as T2238C, is a SNP in the atrial natriuretic precursor A NPPA gene. A large study has been conducted in which 42,418 hypertensive participants 55 or older were followed for several years while on one of four medications: a diuretic, a calcium antagonist, an angiotensin-converting enzyme inhibitor, or an alpha-blocker. The primary endpoint was either fatal heart disease or a heart attack. The blood pressure after six months of rs5065(G;G) patients (note: genotype is in dbSNP orientation, not as published) was lower if the patients were treated with diuretics compared to other medications, with smaller variation seen for (A;A) genotypes. The authors noted that none of the findings retained statistical significance after correction for multiple comparisons, but since the t...

rs351855, a SNP in the fibroblast growth factor receptor 4 (FGFR4) gene, is also known as the Gly388Arg variant. The rs351855(T) allele encodes the risk (Arg) allele. The Arg form of this SNP is likely to cause a harder to treat version of node-positive breast cancer, including reducing the efficacy of Herceptin, based on a study of 372 patients. A study of ~500 Japanese prostate cancer patients found that individuals with a rs351855(T;T) genotype had a 2.2- and 1.9-fold increased risk of prostate cancer and benign prostate hyperplasia (BPH), and a 1.8-fold increased risk of metastatic prostate cancer compared to the (C;C) genotype. A meta-analysis published in 2011, surveying a total of 2,618 cases of prostate cancer, concluded that the odds ratio per rs351855(T) allele was 1.17 (CI: 1.07...

[PharmGKB:In-Depth A study of 124 White patients, which received a high-dose regimen consisting of cyclophosphamide, thiotepa and carboplatin as intravenous infusions, concludes patients homozygous for the GSTP1 C341T allele may have enhanced exposure to thiotepa and tepa.]

[PharmGKB:Curated Risk or phenotype-associated allele: not given. Phenotype: In lymphoblastoid cell lines, this SNP was significantly associated with the IC-50 of cisplatin. Study size/population/ethnicity: lymphoblastoid cell lines from 100 healthy Caucasian-American subjects. Significance metric(s): P = 0.019. Type of association: FA. Also, suggestive, but not significant, evidence was found for association of this SNP with survival of lung cancer patients treated with cisplatin.]

[PharmGKB:Curated A study on 50 subjects (25 patients who developed a distinct hearing loss during cisplatin therapy and in 25 patients without hearing impairment after cisplatin therapy)observed a higher frequency of the A-allele of rs2075252 in the LRP2 in the group with hearing impairment than in the group with normal hearing after cisplatin therapy.]

[PharmGKB:Curated Risk or phenotype-associated allele: None. Phenotype: Variants identified in a screen of 13 genes involved in the gemcitabine drug metabolic pathway. For the non-synonymous CDA:79A>C (K27Q) SNP, the C allele (27Gln) was at frequency 0.36 and 0.04 in Europeans and Africans, respectively. There was a significant difference between ethnic groups in genotype frequency distribution (p < 0.001) Study size: 180. Study population/ethnicity: Healthy, unrelated blood donors of European (n = 95) and African (n = 85) descent. Significance metric(s): p < 0.001. Type of association: GN.]

[PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: In a study of patients with NSCLC on platinum-based treatments, carriers of the A variant of ERCC1:8092C>A had improved outcomes with greater overall survival and median survival times. Study size: 119. Study population/ethnicity: Patients with NSCLC treated with platinum-based regimens as first- or second-line chemotherapy. Significance metric(s): p = 0.009. Type of association: CO.]

rs1800566 (C609T, Pro187Ser) is a snp within NQO1 (NAD(P)H dehydrogenase (quinone 1)). A Ser (T) at this location denotes the NQO1*2 allele. influences the risk of breast cancer according to the 23andMe blog spittoon rs1800566 increases susceptibility to Lung cancer 0.48 times for heterozygotes (CT) [PharmGKB:Curated Risk or phenotype-associated allele: C/T. Phenotype: There was no association between the NQO1*2 polymorphism and the risk of anthracycline-related CHF. Study size: 145. Study population/ethnicity: Nested case-control study was conducted within a cohort of 1979 patients enrolled in the Childhood Cancer Survivor Study who received treatment with anthracyclines and had available DNA. Significance metric(s): OR = 1.04; p = 0.97. Type of association: CO; TOX; ADR.] [OMIM:NAD(P)H ...

[PharmGKB:Curated In a study of ovarian cancer patients (n=104) receiving a cisplatin-cyclophosphamide regimen, the T/T genotype of GSTA1:(-69)C>T polymorphism was associated with increased overall survival.]

[PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: In a study of patients with NSCLC carriers of the C variant of ERCC1:Asn118Asn were more likely to respond to platinum-based chemotherapy compared with those without the C allele. Study size: 119. Study population/ethnicity: Patients with NSCLC treated with platinum-based regimens as first- or second-line chemotherapy. Significance metric(s): OR = 0.10; 95% CI, 0.013-0.828; p = 0.033. Type of association: CO.]

This SNP, in the GSTP1 gene influences asthma risk; the (A) allele encodes the Ile, while the (G) allele encodes the Val. This SNP is also known as GSTP1Val105, or GSTP1 Ile105Val. This research paper shows that 13- to 21-year-olds exposed to tobacco smoke at home, with this mutation had more severe asthma than those without the mutation. rs1695 is also mentioned in this bbc article Several papers published findings associating GSTP1 Ile105Val genotypes with bronchial, childhood, or atopic asthma. Note that some studies, however, have not observed any association between this SNP and asthma in certain populations , or even more paradoxically, have observed that rs1695(G;G) homozygotes appear to be somewhat protected (OR 0.29) from developing asthma compared to individuals with rs1695(A;G) ...

rs13181 is a SNP of the XPD/ERCC2 gene. A meta-analysis of 20 studies, comprising 2,308 cases, ultimately concluded that the rs13181(G) allele is associated with increased cutaneous melanoma risk (odds ratio 1.12, CI: 1.03-1.21, p = 0.01; population attributable risk = 9.6%). [PharmGKB:Curated Risk or phenotype-associated allele: G. Phenotype: The G allele of ERCC2:Lys751Gln was significantly associated with shorter event free survival. Study size: 70. Study population/ethnicity: Patients with osteosarcoma treated with cisplatin; Spain. Significance metric(s): HR = 5.76; 95% CI=1.30-25.55; p = 0.021. Type of association: CO. Phenotype: The G allele of ERCC2:Lys751Gln was significantly associated with decreased response to cisplatin. Study size: 70. Study population/ethnicity: Patients wit...

rs25487 is a SNP also known as Gln399Arg, located in the DNA repair gene XRCC1. The (A) allele encodes the Gln amino acid. In one study of ~1000 Caucasians, the rs25487(A;A) genotype had significantly reduced risk of both basal cell [BCC; odds ratio 0.7, CI: 0.4-1.0] and squamous cell cancer (SCC; odds ratio 0.6, CI: 0.3-0.9). In a study of ~300 Koreans, rs25487(A;G) and (G;G) genotypes had an approximately 2-fold increased risk of basal cell cancer compared to rs25487(A;A) individuals (adjusted odds ratio 2.324, CI: 1.11-4.86, respectively). A small study (113 cases) of Hispanics with non-small cell lung cancer found an odds ratio of 1.52 per rs25487(A) allele (CI: 1.01-2.28). A study of 200 patients with Hodgkin disease compared to controls concluded that some risk was associated with th...

rs2228001, also known as Lys939Gln, K939Q, and K940Q, is a SNP in the DNA nuclear excision repair gene xeroderma pigmentosum complementation group C XPC gene. The Lys (K) allele is encoded by the rs2228001(A) allele. A meta-analysis of 16 studies with 6797 cancer cases and 9018 controls concluded that rs2228001(C;C) homozygotes had an increased overall cancer risk (odds ratio of 1.16, CI: 1.05-1.28) compared with (A;A) homozygotes. This was primarily a risk for lung cancer. [PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.0045 (ANOVA); p = 0.052 (QMIS); p = 0.0004 (KW) Type of association...

This SNP, a variant in the TP53 gene, is 1 of 25 SNPs reported to represent independently minor, but cumulatively significant, increased risk for breast cancer. For details of all 25 SNPs in this group, along with the two methods used to calculate overall risk estimates for breast cancer, refer to the SNPedia breast cancer entry. For this particular SNP, the risk (minor) allele is (C). The minor allele encodes an arginine at position 72 of the protein (where there's normally a proline), and the SNP is commonly called the Arg72 variant, although P72R and Arg72Pro are also common in the literature. Minor allele homozygotes, i.e. rs1042522(C;C) genotypes, live on average 3 years longer than major allele (G;G) homozygotes, based on a study of 9,200+ Danish individuals. The increased longevity ...

[PharmGKB:Curated In a study of ovarian cancer patients (n=104) receiving a cisplatin-cyclophosphamide regimen, the AGG/AGG genotype (insertion) of GSTM3 intron 6 insertion/deletion was associated with decreased incidence of thrombocytopenia, anemia and neuropathy.]

[PharmGKB:Curated In a study of ovarian cancer patients (n=104) receiving a cisplatin-cyclophosphamide regimen, the XPD:312Asp/Asn (G/A) genotype was associated with severe neutropenia.]

spittoon hearing loss linked to a chemotherapy drug named Cisplatin. [PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: This variant was associated with cisplatin-induced hearing loss from a large candidate gene screen in 2 pediatric cohorts.. Study size: 54 (discovery); 112 (replication). Study population/ethnicity: Children with neoplasms receiving cisplatin; Canada. Significance metric(s): OR = 5.52 (CI 1.91, 15.95); p = 0.000182 Type of association: CO; TOX; ADR] [OMIM:?]

[PharmGKB:Non-Curated Increased metformin uptake in transfected cells]

rs1142345 is a SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. In general, individuals must have two nonfunctioning TPMT alleles for the toxicity to be pronounced. The risk allele for this SNP is rs1142345(G), and when it is the only variant in the TPMT gene, it encodes the TPMT*3C allele. While still rare, it is more common in African-Americans (2.4% of all alleles) than in Caucasians. Note that if the same allele also carries the rs1800460(A) SNP, the allele is actually a TPMT*3A allele (OMIM). The medicine 6-Mercaptopurine is metabolized by TPMT. Individual differences in TPMT activity associated with this SNP are now used to determine appropriate dosage range and interval for treatment. spit...

[PharmGKB:Curated Risk or phenotype-associated allele: None. Phenotype: Variants identified in a screen of 13 genes involved in the gemcitabine drug metabolic pathway. For the non-synonymous CDA:208G>A (A70T) SNP, the A allele (70Thr) was at frequency 0.00 and 0.13 in Europeans and Africans, respectively. There was a significant difference between ethnic groups in genotype frequency distribution (p < 0.001) Study size: 177. Study population/ethnicity: Healthy, unrelated blood donors of European (n = 93) and African (n = 84) descent. Significance metric(s): p < 0.001. Type of association: GN.] [OMIM:CYTIDINE DEAMINASE; CDA]

The minor allele (G) of rs25531 is almost always in phase with the long (L) allele of the 5-HTTLPR, which is the most commonly studied variation in this region. The (L) long allele may be associated with lower levels of serotonin. The article and video from 'The Atlantic' suggests that children with the short allele (A), may need and benefit greatly from more maternal support *http://www.theatlantic.com/doc/200912/dobbs-orchid-gene In contrast to earlier reports linking rs25531, a SNP in the serotonin transporter SLC6A4 gene, to obsessive compulsive disorder (OCD), a March 2007 publication finds no significant association studying 'the largest sample size of OCD patients (N=347) and controls (N=749) ever investigated'. A separate study of 75 patients suffering mood disorders after traumati...

In Caucasian non-Hispanics, the rs1360780(T) allele is associated with increased risk for depression, with an odds ratio of 1.39 (CI: 1.14-1.70, p=0.046). This same SNP, which is in the FKBP5 gene, may influence how patients respond to antidepressants including citalopram. rs1360780(T;T) homozgyotes tend to report more depressive episodes, but they also respond better to treatment with antidepressants. rs9296158 rs3800373 rs1360780 rs9470080 linked with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. [PharmGKB:Curated This variant is associated with higher chance of response to anti-depressant drugs.] [OMIM:FK506-BINDING PROTEIN 5; FKBP5]

This SNP, located in an intron of the GRIA3 gene (also known as AMPA3), has been linked in one study to increased thoughts of suicide in patients taking the anti-depressant drug citalopram. The increased risk is calculated to be 1.9x. If the individual is also carrying two rs2518224(C) alleles, i.e. is a rs2518224(C;C) homozygote, the odds ratio for having suicidal thoughts is increased to ~15x (CI: 3.7 - 60.6). [PharmGKB:Curated This SNP in the GRIA3 gene was associated with treatment-emergent suicidal ideation during citalopram therapy in a clinically representative cohort of outpatients with major depressive disorder. DNA samples from 1,915 participants were genotyped.]

[PharmGKB:Curated This variant was shown to be assoicated with antidepressant treatment response in a study consisting of 188 Chinese MDD patients and 346 controls.The G allele was less frequent in responders than nonresponders]

[PharmGKB:Curated This variant is associated with antidepressant treatment response in Chinese major depressive disorder. In a four-locus haplotype analysis (rs334558; rs13321783; rs2319398; rs6808874), the GSK3B TAGT carriers showed a poorer response to antidepressants than carriers with other haplotype groups.]

[PharmGKB:Curated This variant is associated with antidepressant treatment response in Chinese major depressive disorder. In a four-locus haplotype analysis (rs334558; rs13321783; rs2319398; rs6808874), the GSK3B TAGT carriers showed a poorer response to antidepressants than carriers with other haplotype groups.]

rs10248420 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs10248420 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are kn...

[GWAS:Treatment response to citalopram]

[PharmGKB:Curated This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.]

rs11983225 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs11983225 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are kn...

rs4148739 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs4148739 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

[GWAS:Treatment response to citalopram]

Carriers of rs10897346(C) alleles showed a 2.6-fold increased risk (CI: 1.4-4.8) for nonresponse to all major types of anti-depressant drugs (such as the SSRI drug citalopram) in a study of 182 German patients. [PharmGKB:Curated This SNP was significantly associated with response to therapy in 182 patient who received treatment for major depression.]

[PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: The CYP2C19*17 allele was associated with significantly increased metabolism of imipramine. Study size: 178 Study population/ethnicity: Psychiatric patients aged 18-65 with a score of greater than or equal to 17 on the Hamilton Rating Scale for Depression. Significance metric(s): p = 0.035 Type of association: PK]

Although not associated with increased risk for developing bipolar disorder, amongst those with it, the (G) allele of this SNP has been reported to have a somewhat protective effect in that individuals who have a (G) allele develop bipolar disorder at a later age than those with the more common (A;A) genotypes. Also known as the -50T/C SNP from this GSK3-beta (GSK3B) gene. may effect lithium treatment response - C allele carriers showed considerably greater response with lithium treatment, with remissions of 56.25% after 4 weeks compared to 31% for T/T carriers [PharmGKB:Curated This variant is in the promoter region of GSK3B. T allele is associated with greater transcription activity compared with the A allele. This variant is associated with antidepressant treatment response in Chinese ...

rs4148740 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs4148740 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs4675690 is in close proximity to CREB1, and adjacent to LOC151194. g2b2mh blog individuals with the TT genotype at rs4675690 (C/T) showed less disgust, but not happiness, desire or fear. T allele associated with increased chance of suicide (OR = 2.3, 95% CI 1.3-2.9, TT homozygotes vs CC homozygotes?) during the first 30 days (p > 0.05 after the first month) of citalopram treatment, in a study of 1447 citalopram users (male only subgroup, 539 in total). Two haplotypes (see below) also showed significant association with suicidality in the male subgroup. *rs2709376(C),rs2253206(A),rs7569963(A),rs7594560(T),rs4675690(C) - common haplotype, reduced chance of suicide in males, p = 0.004 *rs2709376(C),rs2253206(A),rs7569963(G),rs7594560(T),rs4675690(T) - increased chance of suicide in males...

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

[GWAS:Treatment response to citalopram]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

rs7997012, located in an intron of the HTR2A gene, was found to be associated with a somewhat increased rate of successful response to treatment of depression with the drug citalopram. From this article : 'HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram. Participants who were homozygous for the A allele had an 18% reduction in absolute risk of having no response to treatment, compared with those homozygous for the other allele.' * See also Anxiety Blog posting [PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: Patients with the 5-HTR2A intron 2 (rs7997012) AA genotype suffered from more pronounced side effects compared to carriers of the GA or GG genotype. Study size: 124. Study population/ethnicity: Caucasian; Patients with psychiatric diso...

[GWAS:Treatment response to citalopram]

rs7569963 is directly adjacent to CREB1. Associated with significantly (p = 0.005) increased chance of suicide in a study of 1447 citalopram users (male only subgroup, 539 in total). Two haplotypes (see below) also showed significant association with suicidality in the male subgroup. *rs2709376(C),rs2253206(A),rs7569963(A),rs7594560(T),rs4675690(C) - common haplotype, reduced chance of suicide in males, p = 0.004 *rs2709376(C),rs2253206(A),rs7569963(G),rs7594560(T),rs4675690(T) - increased chance of suicide in males, p = 0.009 [PharmGKB:Curated In a nested case-control study derived from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study this SNP in the CREB1 gene was associated with treatment-emergent suicidality among men with depression.]

[GWAS:Treatment response to citalopram]

[PharmGKB:Curated This variant is associated with antidepressant treatment response in Chinese major depressive disorder. In a four-locus haplotype analysis (rs334558; rs13321783; rs2319398; rs6808874), the GSK3B TAGT carriers showed a poorer response to antidepressants than carriers with other haplotype groups.]

rs1954787, located in an intron of the GRIK4 gene, was found to be associated with a somewhat increased rate of successful response to treatment of depression with the drug citalopram. From the abstract of this article: 'The effect size of (this) GRIK4 marker alone was modest, but homozygote carriers of the treatment-response-associated marker alleles of both the GRIK4 and HTR2A (see rs7997012) genes were 23% less likely to experience nonresponse to (citalopram) treatment relative to participants who did not carry any of these marker alleles.' * See also Anxiety Blog posting [PharmGKB:Curated A study in 1,816 eligible patients from the STAR*D cohort found that genetic variation in a kainic acid-type glutamate receptor is reproducibly associated with response to the antidepressant citalopr...

rs7787082 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs7787082 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs12720067 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs12720067 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are kn...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235015 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is near 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. rs2235015 has an r² value of >0.5 with this group. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported ...

rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235040 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2235067 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2235067 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

This SNP, located in an intron of the GRIK2 gene, has been linked in one study to increased thoughts of suicide in patients using the anti-depressant drug citalopram. The risk is only seen for individuals carrying two rs2518224(C) alleles, i.e. the rs2518224(C;C) homozygotes. The odds ratio for these individuals is 8.2. If the individual also has at least one rs4825476(G) allele, the odds ratio for having suicidal thoughts is increased to ~15x (CI: 3.7 - 60.6). [PharmGKB:Curated This SNP in the GRIK2 gene was associated with treatment-emergent suicidal ideation during citalopram therapy in a clinically representative cohort of outpatients with major depressive disorder. DNA samples from 1,915 participants were genotyped.]

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. A study of 1,000+ breast cancer patients showed a 0.77x decreased risk of breast cancer for carriers of a CYP2C19*17 allele (CI: 0.65-0.93, p = 0.005). Analysis of a subgroup of such carriers who were using hormone therapy for ten years or longer showed an even stronger effect (odds ratio 0.57, CI: 0.39-0.83, p = 0....

[PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: The CYP2C19*17 allele was associated with significantly increased metabolism of imipramine. Study size: 178 Study population/ethnicity: Psychiatric patients aged 18-65 with a score of greater than or equal to 17 on the Hamilton Rating Scale for Depression. Significance metric(s): p = 0.035 Type of association: PK]

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. A study of 1,000+ breast cancer patients showed a 0.77x decreased risk of breast cancer for carriers of a CYP2C19*17 allele (CI: 0.65-0.93, p = 0.005). Analysis of a subgroup of such carriers who were using hormone therapy for ten years or longer showed an even stronger effect (odds ratio 0.57, CI: 0.39-0.83, p = 0....

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

rs351855, a SNP in the fibroblast growth factor receptor 4 (FGFR4) gene, is also known as the Gly388Arg variant. The rs351855(T) allele encodes the risk (Arg) allele. The Arg form of this SNP is likely to cause a harder to treat version of node-positive breast cancer, including reducing the efficacy of Herceptin, based on a study of 372 patients. A study of ~500 Japanese prostate cancer patients found that individuals with a rs351855(T;T) genotype had a 2.2- and 1.9-fold increased risk of prostate cancer and benign prostate hyperplasia (BPH), and a 1.8-fold increased risk of metastatic prostate cancer compared to the (C;C) genotype. A meta-analysis published in 2011, surveying a total of 2,618 cases of prostate cancer, concluded that the odds ratio per rs351855(T) allele was 1.17 (CI: 1.07...

[PharmGKB:In-Depth A study of 124 White patients, which received a high-dose regimen consisting of cyclophosphamide, thiotepa and carboplatin as intravenous infusions, concludes patients homozygous for the GSTP1 C341T allele may have enhanced exposure to thiotepa and tepa.]

rs9561778 is a SNP in the ATP-binding cassette, sub-family C (CFTR/MRP), member 4 ABCC4 gene. A stepwise case-control study of ~400 breast cancer Japanese patients receiving cyclophosphamide-based combination chemotherapy, roughly divided equally between those having or not having serious adverse drug reactions (ADRs), concluded that carriers of rs9561778(T) allele had a ~2x higher risk of ADRs. The ADRs for these patients tended to be gastrointestinal toxicity and leukopenia/neutropenia. [PharmGKB:Curated Risk or phenotype-associated allele: T. Phenotype: In a stepwise case-control association study of breast cancer patients receiving cyclophosphamide combination therapy, rs9561778 in ABCC4 was associated with cyclophosphamide-induced ADRs. Study size: 403. Study population/ethnicity: Ja...

[PharmGKB:In-Depth Risk or phenotype-associated allele: T. Phenotype: CYP2B6*6 genotype of the transplant donor was associated with toxicity and venoocclusive disease of the liver in the recipient. Study size:107 . Study population/ethnicity: Donors and patients with leukemia after HLA-identical hematopoietic stem cell transplantation, France. Significance metric(s): p = 0.03. Type of association: TOX]

[PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: In a study of patients with NSCLC on platinum-based treatments, carriers of the A variant of ERCC1:8092C>A had improved outcomes with greater overall survival and median survival times. Study size: 119. Study population/ethnicity: Patients with NSCLC treated with platinum-based regimens as first- or second-line chemotherapy. Significance metric(s): p = 0.009. Type of association: CO.]

[PharmGKB:Curated In a study of ovarian cancer patients (n=104) receiving a cisplatin-cyclophosphamide regimen, the T/T genotype of GSTA1:(-69)C>T polymorphism was associated with increased overall survival.]

[PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: In a study of patients with NSCLC carriers of the C variant of ERCC1:Asn118Asn were more likely to respond to platinum-based chemotherapy compared with those without the C allele. Study size: 119. Study population/ethnicity: Patients with NSCLC treated with platinum-based regimens as first- or second-line chemotherapy. Significance metric(s): OR = 0.10; 95% CI, 0.013-0.828; p = 0.033. Type of association: CO.]

This SNP, in the GSTP1 gene influences asthma risk; the (A) allele encodes the Ile, while the (G) allele encodes the Val. This SNP is also known as GSTP1Val105, or GSTP1 Ile105Val. This research paper shows that 13- to 21-year-olds exposed to tobacco smoke at home, with this mutation had more severe asthma than those without the mutation. rs1695 is also mentioned in this bbc article Several papers published findings associating GSTP1 Ile105Val genotypes with bronchial, childhood, or atopic asthma. Note that some studies, however, have not observed any association between this SNP and asthma in certain populations , or even more paradoxically, have observed that rs1695(G;G) homozygotes appear to be somewhat protected (OR 0.29) from developing asthma compared to individuals with rs1695(A;G) ...

The rs4880(T) allele, part of the codon for amino acid valine at codon 16 of the antioxidant protein from the mitochrondrial superoxide dismutase 2 SOD2 gene, is the most common in most populations studied. The rs4880(C) allele gives rise to an alanine at this position. There appears to be some conflict in the literature over the effect of this SNP. Having a valine at codon 16 is said to reduce enzyme activity , and thus lead to increased oxidative stress, yet in at least one study of the actual enzyme levels measured in people, SOD2 activity was 33% higher in (C;T) or (T;T) individuals compared to (C;C) individuals . Regardless of how this resolves, several phenotypic associations have been reported for this SNP, including: * A 10 fold higher risk for heart disease in hereditary hemochrom...

rs25487 is a SNP also known as Gln399Arg, located in the DNA repair gene XRCC1. The (A) allele encodes the Gln amino acid. In one study of ~1000 Caucasians, the rs25487(A;A) genotype had significantly reduced risk of both basal cell [BCC; odds ratio 0.7, CI: 0.4-1.0] and squamous cell cancer (SCC; odds ratio 0.6, CI: 0.3-0.9). In a study of ~300 Koreans, rs25487(A;G) and (G;G) genotypes had an approximately 2-fold increased risk of basal cell cancer compared to rs25487(A;A) individuals (adjusted odds ratio 2.324, CI: 1.11-4.86, respectively). A small study (113 cases) of Hispanics with non-small cell lung cancer found an odds ratio of 1.52 per rs25487(A) allele (CI: 1.01-2.28). A study of 200 patients with Hodgkin disease compared to controls concluded that some risk was associated with th...

The NOS3 gene encodes nitric oxide synthase 3, and is also known as eNOS; rs2070744 is a SNP in the promoter region that is associated with higher levels of the corresponding mRNA (and possibly protein). Associations for the risk allele (C) of this SNP include: * Rheumatoid Arthritis , and, * cardiovascular mortality in high-risk patients * Progression (but not occurence) of prostate cancer Men who carry the C allele responded more favorably to the antihypertensive effects of aerobic exercise Current HapMap data for this snp appears wrong (ss42994451). The population diversity information is instead being estimated based on ss48295994 P1, and should be replaced what a new HapMap ss# is available. [PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: Subjects carrying the eN...

This SNP, a variant in the TP53 gene, is 1 of 25 SNPs reported to represent independently minor, but cumulatively significant, increased risk for breast cancer. For details of all 25 SNPs in this group, along with the two methods used to calculate overall risk estimates for breast cancer, refer to the SNPedia breast cancer entry. For this particular SNP, the risk (minor) allele is (C). The minor allele encodes an arginine at position 72 of the protein (where there's normally a proline), and the SNP is commonly called the Arg72 variant, although P72R and Arg72Pro are also common in the literature. Minor allele homozygotes, i.e. rs1042522(C;C) genotypes, live on average 3 years longer than major allele (G;G) homozygotes, based on a study of 9,200+ Danish individuals. The increased longevity ...

[PharmGKB:Curated In a study of ovarian cancer patients (n=104) receiving a cisplatin-cyclophosphamide regimen, the AGG/AGG genotype (insertion) of GSTM3 intron 6 insertion/deletion was associated with decreased incidence of thrombocytopenia, anemia and neuropathy.]

[PharmGKB:Curated In a study of ovarian cancer patients (n=104) receiving a cisplatin-cyclophosphamide regimen, the XPD:312Asp/Asn (G/A) genotype was associated with severe neutropenia.]

rs1799983 (also known as Glu298Asp, E298D, or G894T) located in the NOS3 gene was associated with an ~2x risk (p=0.006) of developing pre-eclampsia (pregnancy-induced hypertension) and further complications of it in a study of ~50 African women. A large meta-analysis combining 26 studies (9,867 patients) found that homozygosity for rs1799983(T;T) increases risk of ischemic heart disease. The odds ratio was 1.31 (CI: 1.13-1.51). However, a study of 1,600 Greek patients concluded that rs1799983 was not associated with risk of acute myocardial infarction in that population. left ventricular hypertrophy in human essential hypertension OR=1.5 [PharmGKB:Curated Risk or phenotype-associated allele: T. Phenotype: Women assigned to chemotherapy who had NOS3 −786 CC and 894 TT genotypes had a...

rs1056836, also known as 4326C/G, Val432Leu or L432V, is a SNP in the cytochrome P450 1B1 (CYP1B1) gene. This gene is a member of the CYP1 gene family and one of the major enzymes involved in the hydroxylation of estrogens, a reaction likely to be relevant in hormonal carcinogenesis. [In dbSNP orientation, the (C) allele encodes the Leu; the (G) the Val.] In a study of 153 Hispanic Caucasians with prostate cancer the rs1056836(G;G) genotype showed decreased risk compared to the more common (C;C) genotype (odds ratio = 0.31, p = 0.04, CI: 0.10-0.96). This report cites another study as indicating that rs1056836(C;C) high-risk stage III and IV breast cancer patients receiving dose-intense paclitaxel in combination with doxorubicin and cyclophosphamide experience a longer progression-free surv...

[PharmGKB:Curated Risk or phenotype-associated allele: T. Phenotype: CYP2B6*2 genotype in the transplant recipient was associated with hemorrhagic cystitis. Study size:107 . Study population/ethnicity: Donors and patients with leukemia after HLA-identical hematopoietic stem cell transplantation, France. Significance metric(s): p = 0.03. Type of association: TOX]

rs2279343, also known as Lys262Arg, is a SNP within the CYP2B6 gene. variants including the Arg allele include CYP2B6*4, CYP2B6*6, and CYP2B6*7 [PharmGKB:In-Depth Risk or phenotype-associated allele: G. Phenotype: CYP2B6*4 genotype in the transplant recipient was associated with oral mucositis. Study size:107 . Study population/ethnicity: Donors and patients with leukemia after HLA-identical hematopoietic stem cell transplantation, France. Significance metric(s): p = 0.0067. Type of association: TOX]

The rs2740574(G) allele encodes a variant form of CYP3A4 known as CYP3A4*1B. rs2740574(G) alleles are associated with an ~10 fold higher risk of aggressive prostate cancer in African American males. [PMID 16414488, OMIM A pooled study (1,400+ samples) along with a replication study conducted by members of the Ovarian Cancer Association Consortium found a 2.5-2.8x increased risk for ovarian cancer] for rs2740574(G;G) individuals (CI: 1.2-6.5, p=0.017). The authors note that CYP3A4 encodes a key enzyme in estrogen metabolism and which may be linked to ovarian carcinogenesis. [PharmGKB:Curated Risk or phenotype-associated allele: CYP3A4*1B, rs2740574 G allele. Phenotype: CYP3A4*1B (rs2740574 G) allele carriers show a significantly increased risk for SCLC (OR = 2.25, p = 0.02), which showed a...

rs762551, also known as -164A>C or -163C>A, is a SNP encoding the CYP1A2*1F allele of the CYP1A2 gene. For historic reasons, the rs762551(C) allele is considered the wild-type, even though it is the rarer allele in most populations. The rs762551(A) allele is the 'fast metabolizer' allele known as CYP1A2*1F; the (C) allele is by comparison a slower metabolizer of certain substrates (including caffeine). In terms of genotypes, only rs762551(A;A) individuals are considered fast metabolizers. Individuals who are rs762551(A;C) heterozygotes or rs762551(C;C) homozygotes are both considered slow metabolizers. The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. One well known substrate of CYP1A2 is caffeine; individuals who are ca...

Variation at this SNP, rs5751876, also referred to as 1976C>T or 1976T>C, appears to influence how an individual responds to moderate levels (150mg) of caffeine, with T/T carriers displaying significantly increased subjective levels of anxiety after consumption. rs5751876 is not associated with how much coffee one drinks, though, nor with risk for Parkinson's disease, based on a study of 1,200 subjects.

Variation at this SNP, rs2298383, appears to influence how an individual responds to moderate levels (150mg) of caffeine. [PharmGKB:Curated Risk or phenotype-associated allele: rs2298383 T allele. Phenotype: Carriers of 1 or 2 copies of the T allele for rs2298383 showed increased risk of any (OR = 2.23, CI 1.03-5.07, p = 0.03) or gastrointestinal-specific (OR = 2.65, CI = 0.8-11.35, p = 0.09) adverse events. Study size: 309 RA patients, including 147 good MTX responders, 101 MTX inefficacy failures, and 61 adverse event (AE) MTX failures (e.g. gastrointestinal (n = 24), abnormal liver function tests (n = 20), haematological (n = 7), skin rashes (n = 6), and other (n = 17). Study population/ethnicity: Rheumatoid arthritis (RA) patients aged over 18 yrs, of White Caucasian ethnic origin, cl...

rs4410790 and rs2470893 influences habitual caffeine consumption

rs4410790 and rs2470893 influence habitual caffeine consumption

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs1045642, also known as C3435T, is a SNP located in the ABCB1 gene. It is often studied in conjunction with rs2032582. C3435T has been mentioned by: * A 'Silent' Polymorphism in the MDR1 Gene Changes Substrate Specificity (for example, to verapamil) * (R)-lansoprazole (Prevacid) concentrations are significantly increased in CYP2C19 extensive metabolizers with ABCB1 C3435T C allele. * In a Korean population, plasma concentrations of fexofenadine (Allegra) were 17% lower in 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects compared to 2677GG/3435CC subjects. * In contrast, in this study no association was observed between the C3435T polymorphism and fexofenadine plasma or urine concentrations in a German Caucasian population. * A meta-analysis including 9 case-control stud...

rs10935838, rs2046934, rs5853517, and rs6809699 venous thromboembolism lower risk of incident DVT/PE as compared to the reference haplotype H1 (odds ratio=0.50, 95% CI=0.27-0.93, p=0.028) [PharmGKB:Curated This SNP was used to tag the H2 haplotype to show association with peripherial arterial disease and coronary artery disease.]

JAMA rs12777823 and rs4244285 implicated in platelet response to clopidogrel [PharmGKB:Curated A GWAS found this variant (rs12777823) was the most significantly associated SNP with clopidogrel response. This SNP was in strong linkage disequilibrium with 12 further SNPs within the CYP2C18-CYP2C19-CYP2C9-CYP2C8 cluster (rs12777823; rs10109204; rs2025445; rs1326837; rs717238; rs2860838; rs2860903; rs9332105; rs9332113; rs12572351; rs10509679; rs1934951; rs1934680) and also with the loss-of-function variant CYP2C19*2 (rs4244285). Further findings in this study showed that the CYP2C19*2 genotype accounted for most of all the initially found association with diminished platelet response to clopidogrel.]

rs3842787, also known as 50C>T, is a SNP in the signal peptide region of the cyclooxygenase-1 PTGS1 gene. A study of 696 European patients undergoing elective diagnostic coronary angiographies (CAGs) because of suspected or proven stable coronary artery disease found that 23 experienced bleeding, perhaps the most common complication of this type of invasive coronary procedure. After controlling for various variables (especially gender), two co-inherited SNPs, rs10306114 and rs3842787, were found to be associated with higher risk for bleeding in otherwise low risk patients who (i) did undergo percutaneous coronary intervention and (ii) did not take clopidogrel. Having the less common haplotype (rs10306114(G) and/or rs3842787(T)) increases the bleeding risk upon CAG ~12 fold (p = 0.012). ...

rs10306114, also known as -842A>G, is a SNP upstream of the cyclooxygenase-1 PTGS1 gene. A study of 696 European patients undergoing elective diagnostic coronary angiographies (CAGs) because of suspected or proven stable coronary artery disease found that 23 experienced bleeding, perhaps the most common complication of this type of invasive coronary procedure. After controlling for various variables (especially gender), two co-inherited SNPs, rs10306114 and rs3842787, were found to be associated with higher risk for bleeding in otherwise low risk patients who (i) did undergo percutaneous coronary intervention and (ii) did not take clopidogrel. Having the less common haplotype (rs10306114(G) and/or rs3842787(T)) increases the bleeding risk upon CAG ~12 fold (p = 0.012).

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. A study of 1,000+ breast cancer patients showed a 0.77x decreased risk of breast cancer for carriers of a CYP2C19*17 allele (CI: 0.65-0.93, p = 0.005). Analysis of a subgroup of such carriers who were using hormone therapy for ten years or longer showed an even stronger effect (odds ratio 0.57, CI: 0.39-0.83, p = 0....

rs28399504 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*4 variant. This variant has been linked to poor metabolism of compounds like mephenytoin. It is also known as M1V or Met1Val. The risk allele is rs28399504(G). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). According to a 23andMe discussion This is one of the SNPs which were re-analyzed April 2009. Customers with older data may wish to redownload. SNPs effected rs4420638, rs34276300, rs3091244, rs34601266, rs2033003, rs7900194, rs9332239, rs28371685, rs1229984, and rs28399504. [PharmGKB:Curated Subjects ...

Defines the CYP2C19 variant known as CYP2C19*8. Carriers of the rs41291556(C) allele may have decreased activity and poor metabolizer (PM) phenotype. This variant is associated with a dramatic (approximately 90% and 70%) reduction in the metabolism of S-mephenytoin and tolbutamide in vitro. [PharmGKB:Curated This variant is the defining SNP for CYP2C19*8 and leads to decreased activity and poor metabolizer (PM) phenotype.This variant is associated with a dramatic (approximately 90% and 70%) reduction in the metabolism of S-mephenytoin and tolbutamide in vitro.]

rs4244285 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*2 variant. This variant is the most common reason for poor metabolism of compounds like mephenytoin (an anti-convulsant), some antidepressants, the anti-platelet drug Plavix, and some drugs used for ulcer conditions of various types. The risk allele is rs4244285(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (trade name Prevacid). In Caucasians, SNPs in CYP2C19 are relatively rare (in contrast to SNPs in CYP2D6), but SNPs in this gene are common in Asians. Ulcer treatment with omeprazole to reduce Helicobacter pyl...

rs4986893 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*3 variant. This variant has been linked to poor metabolism of compounds like mephenytoin as well as proguanil, and it therefore has implications for malaria prophylaxis. The risk allele is rs4986893(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). [PharmGKB:Curated In contrast to other PPIs, esomeprazole-induced healing of GERD appears to be unrelated to the CYP2C19*3 variant.] [OMIM:MEPHENYTOIN, POOR METABOLISM OF]

The rs72558186(A) SNP represents a CYP2C19 allele known as CYP2C19*7; it reflects a splice donor mutation that leads to a poor metabolizer phenotype. This SNP is also known as CYP2C19_19294T>A, and in the Affymetrix DMET panel, as DMET3B10072. Note: absence of allele frequency data leaves this as a possible ambiguous flip.

rs1057868, also known as A503V, is a relatively common variant defining the POR*28 allele of the P450 (cytochrome) oxidoreductase POR gene. The POR gene encodes a protein involved in electron transport of cytochrome p450 enzymes such as CYP3A4, CYP3A5 and CYP3A7. A study of 251 individuals from two independent studies (182 patients treated with methadone and 69 patients with clozapine) for CYP3A activity found that CYP3A SNPs themselves did not predict particularly well inter-individual variability in overall CYP3A activity. However, rs1057868(T;T) individuals had a 1.6x increased CYP3A activity compared to rs1057868(C) carriers (n=182, p=0.004), and the finding was replicated in a second independent dataset. The authors conclude that this POR gene SNP is a better predictor of overall CYP3...

[PharmGKB:Curated Risk or phenotype-associated variant: G. Phenotype: The A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with atypical antipsychotic-induced obsessive compulsive symptoms. Study size: 94. Study population/ethnicity: Patients with schizophrenia receiving atypical antipsychotics; Asian; Korea. Significance metric(s): p = 0.04. Type of association: CO.]

[PharmGKB:Curated Risk or phenotype-associated variant: A. Phenotype: The A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with atypical antipsychotic-induced obsessive compulsive symptoms. Study size: 94. Study population/ethnicity: Patients with schizophrenia receiving atypical antipsychotics; Asian; Korea. Significance metric(s): p = 0.04. Type of association: CO.]

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 3 x 10^-7 for triglycerides as a result of clozapine use

[PharmGKB:Curated Risk or phenotype-associated allele: C Phenotype: Patients homozygous for the rs4436578-C allele were at increased risk of body weight gain as compared with the heterozygotes and those of the rs4436578-TT genotype after atypical antipsychotics treatment Study size: 479 chronic inpatients with schizophrenia Study population/ethnicity: Chinese Significance metric(s): OR = 3.36 (95% confidence interval=1.62 approximately 7.00) Type of association: GN]

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 4 x 10^-7 for total cholesterol as a result of clozapine use

[PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: The C allele was associated with weight gain of at least 7% in schizophrenia patients treatment with clozapine or olanzapine. Study size: 206. Study population/ethnicity: European american; African American; German; Schizophrenia. Significance metric(s): OR = 3.44 (CI: 1.46-8.11). Type of association: PD.]

rs1799732 is a SNP in the D2 dopamine receptor gene DRD2 gene. Although dbSNP indicates the alleles as (C) or (-) (i.e. a deletion), investigators report the alleles as (C) or (T). In a study of individuals in the Polyp Prevention Trial with any, multiple (>/=2) or advanced colorectal adenoma recurrence after 4 years, compared to those without adenoma recurrence, rs1799732(C;T) individuals were significantly associated with all adenoma recurrence (odds ratio 1.30, CI: 1.01-1.69). The authors speculate this increased risk of adenoma recurrence (and an association with colorectal cancer) may be related to SNP-associated differences in alcohol and fat intake. spittoon Alcoholism related *rs1799971(A;A) severe alcoholism 2x *rs1799732(I;I) severe alcoholism 1.85x [PharmGKB:Curated Risk or ...

may be associated with clozapine response in treatment-resistant schizophrenic patients [PharmGKB:Curated Patients with diplotype ACCCTC/GTTGCC, genotypes T/T+T/C, or allele T of marker rs742105 showed a better response to clozapine (0.005</=P</=0.049) in a study of patients with refractory schizophrenia.]

rs6277 (957C>T, Pro319Pro) is one of several SNPs in the dopamine receptor DRD2 gene. In a study of 300+ Russian patients with schizophrenia, the rs6277(C) allele was associated with higher risk. From a pooled meta-study (total of 4 other reports plus this one) the allelic odds ratio is 1.42 (CI: 1.26-1.61, p<0.00005), and the genotypic odds ratio for the (C;C) genotype was 1.6 (CI: 1.32-1.95, p<0.00005). Note that rs6275 and rs6277 are only 18bp apart, hence their very tight linkage (r²=1). C allele associated significantly (p = 0.021) with post-traumatic stress disorder in a sample of (assumedly Australian) 127 war veterans w/ 228 controls spittoon people with two As at rs6277(T;T) were better at NoGo learning. [pharmgkb] T allele associated with decrease ...

rs1414334(C) associated with the metabolic syndrome in patients using *clozapine (OR, 9.20; 95% CI, 1.95-43.45) *risperidone (OR, 5.35; 95% CI, 1.26-22.83) [PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: In a replication study, the C allele of HTR2C rs1414334 polymorphism is associated with development of the metabolic syndrome during treatment with antipsychotics. Study size: 186. Study population/ethnicity: 93% Caucasian; European; Dutch; The Netherlands. Significance metric(s): OR = 3.73; 95% CI= 1.29-10.79; P = 0.015. Type of association: CO.]

[PharmGKB:Curated Risk or phenotype-associated variant: C. Phenotype: The A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with atypical antipsychotic-induced obsessive compulsive symptoms. Study size: 94. Study population/ethnicity: Patients with schizophrenia receiving atypical antipsychotics; Asian; Korea. Significance metric(s): p = 0.04. Type of association: CO.]

In mice, the genetic locus best correlated to anxiety-related behaviour contains the 'regulator of G protein signaling 2' gene . In humans, SNPs in the equivalent RGS2 gene have now been studied to see if they are correlated to anxiety related disorders. In the first part of one study, 119 families including children underwent standard lab-based behavioural assessments of behavioural inhibition, defined as a heritable temperamental profile characterized by a tendency to be shy, avoident, and behaviourally restrained in situations that are novel or unfamiliar. Along with some other RGS2 SNPs, carriers of a rs4606(G) allele were 3 fold more likely to exhibit behavioural inhibition (CI: 1.31-6.84, p = 0.0026). In the second part of this study, 744 college undergraduates (228 men, 516 women) w...

rs6280, also known as '''Ser9Gly''', is a SNP in the dopamine receptor D3 DRD3 gene. The rs6280(C) allele encodes a glycine, and the (T) allele encodes a serine (in dbSNP orientation). In a study of 88 patients being treated for schizophrenia with olanzapine, those who were rs6280(C;C) homozygotes had greater positive symptom remission (endpoint rating of minimal or none on all PANSS clinical response positive items, 39.1%), as compared with (C;T) or (T;T) genotypes (13.8%; p = 0.033). Ser9Gly has been implicated in executive function in some studies, but the results are conflicting. * Gly/Gly carriers showed significantly (p = 0.002) poorer performance than Ser/Ser carriers on executive functioning tasks in a somewhat small Caucasian sample (84 patients with first-episode psychosis and 85...

rs1800497, a SNP also known as the TaqIA (or Taq1A) polymorphism of the dopamine D2 receptor DRD2 gene (even though it is actually located over 10,000bp downstream of the gene), gives rise to the DRD2*A1 allele. This allele (rs1800497(T)) is associated with a reduced number of dopamine binding sites in the brain , and has been postulated to play a role in alcoholism, smoking, and certain neuropsychiatric disorders. The reduced number of dopamine binding sites may play a role in nicotine addiction by causing an 'understimulated' state that can be relieved by smoking (and/or use of other drugs). A wide variety of reports have been published over more than ten years either linking rs1800497 to aspects of nicotine use and smoking cessation success, or finding no such association. A meta-analys...

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 6 x 10^-8 for triglycerides as a result of clozapine use

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 3 x 10^-6 for triglycerides as a result of clozapine use

rs5443, a SNP in the G-protein beta3 subunit (GNB3) gene that is more commonly known as the C825T variant, has been linked to a number of metabolic conditions including obesity, coronary artery disease, insulin resistance and therefore diabetes, left ventricular hypertrophy, and hypertension. It has also been linked to how well a patient responds to Viagra (sildenafil). Several studies have been unable to replicate one or more of the associations in at least some populations between this SNP and these conditions. The more notable studies include: *rs5443(T) allele carriers are 2-3 fold more likely to be obese in Caucasian, Chinese, and African American populations. *rs5443(T) carriers are clearly at higher risk for hypertension, but this review indicates that whether they are also at incre...

rs72547517, also known as 5166G>A, 5347T>C or R456H, is a SNP in the CYP1A2 gene. The rs72547517(A) allele defines the CYP1A2*8 variant. [PharmGKB:Curated Risk or phenotype-associated allele: A Phenotype: In an in vitro system, this variant showed no activity for the drug substrates clozapine or phenacetin even at the highest substrate and double membrane concentrations, it also showed reduced expression of holoprotein in bacterial cells. Type of association: FA]

rs72547516, also known as 2499A>T or I386F, is a SNP in the CYP1A2 gene. The rs72547516(T) allele defines the CYP1A2*4 variant. [PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: In an in vitro system, this variant showed no activity for the drug substrates clozapine or phenacetin even at the highest substrate and double membrane concentrations, it also showed reduced expression of holoprotein in bacterial cells. Type of association: FA]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

The (-) form of this SNP, representing a deletion of one nucleotide, causes a frameshift such that the resulting CYP2D6 protein is nonfunctional. The associated allele is also known as CYP2D6*6, and there are several subtypes but they are all nonfunctional. If two copies of this (or similar) changes are inherited, CYP2D6 poor metabolism ('PM') is observed. CYP2D6 poor metabolism may affect the efficacy or degree of side effects of drugs metabolized by CYP2D6, such as dextromorphan, sparteine, nortriptyline, venlafaxine and codeine. [PharmGKB:Curated This variant is part of the CYP2D6*6 PM haplotype. Plasma concentrations of metoprolol were shown to be were 4.9-fold higher in the PMs, with greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in...

The rs1799971(G) allele in exon 1 of the mu opiod receptor OPRM1 gene causes the normal amino acid at residue 40, asparagine (Asn), to be replaced by aspartic acid (Asp). In the literature this SNP is also known as A118G, N40D, or Asn40Asp. Carriers of at least one rs1799971(G) allele appear to have stronger cravings for alcohol than carriers of two rs1799971(A) alleles, and are thus hypothesized to be more at higher risk for alcoholism. However, subsequent research results are mixed, and there are other studies both agreeing or disagreeing with this finding Among 200+ alcoholics treated with naltrexone, rs1799971(G) carriers receiving the drug (even without behavioral intervention) had an increased percentage of days abstinent (p = .07) and a decreased percentage of heavy drinking days (p...

The wild type (normal) allele at this SNP is (C). The (T) variant indicates the presence of a non-wild type CYP2D6 variant, but it appears in many different variants so it can not be used to determine the presence of any particular variant. The most common variants it appears in are CYP2D6*10 and CYP2D6*4, but these are not the only ones. While this is the defining mutation for CYP2D6*10, it is not possible by itself for this mutation to determine a particular variant. In addition, the CYP2D6*4 variant includes this mutation, but the defining mutation 1846G>A SNP is not available in the common direct to consumer testing services. While it is not possible for this mutation to identify one particular variant, all the variants in which it appears have reduced or no CYP2D6 activity. If two ...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

In Caucasian non-Hispanics, the rs1360780(T) allele is associated with increased risk for depression, with an odds ratio of 1.39 (CI: 1.14-1.70, p=0.046). This same SNP, which is in the FKBP5 gene, may influence how patients respond to antidepressants including citalopram. rs1360780(T;T) homozgyotes tend to report more depressive episodes, but they also respond better to treatment with antidepressants. rs9296158 rs3800373 rs1360780 rs9470080 linked with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. [PharmGKB:Curated This variant is associated with higher chance of response to anti-depressant drugs.] [OMIM:FK506-BINDING PROTEIN 5; FKBP5]

rs9296158 rs3800373 rs1360780 rs9470080 linked with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. [PharmGKB:Curated This variant is associated with higher chance of response to anti-depressant drugs.]

[PharmGKB:Curated Based on an study on 284 Mexican Americans, this variant in the 3' UTR of TBX21 is significantly associated with major depressive disorder (MDD). The results implicate that the specific UTR variation increases the risks for a T-cell dysfunction in MDD in the studied population.]

[PharmGKB:Curated Based on an study on 284 Mexican Americans, this variant in the 5' UTR of PSMB4 is significantly associated with major depressive disorder (MDD). The results implicate that the specific UTR variation increases the risks for a T-cell dysfunction in MDD in the studied population.]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

rs5558 (F528C) is a non-synonymous SNP in SLC6A2 (norepinephrine transporter), with a T encoding for Phenylalanine and C encoding the rare Cysteine variant. assoc. w/ major depression Cysteine variant exhibited increased norepinephrine transport, insensitivity to protein kinase C induced down-regulation, and a decrease in desipramine (tricyclic antidepressant) potency

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

The (-) form of this SNP, representing a deletion of one nucleotide, causes a frameshift such that the resulting CYP2D6 protein is nonfunctional. The associated allele is also known as CYP2D6*6, and there are several subtypes but they are all nonfunctional. If two copies of this (or similar) changes are inherited, CYP2D6 poor metabolism ('PM') is observed. CYP2D6 poor metabolism may affect the efficacy or degree of side effects of drugs metabolized by CYP2D6, such as dextromorphan, sparteine, nortriptyline, venlafaxine and codeine. [PharmGKB:Curated This variant is part of the CYP2D6*6 PM haplotype. Plasma concentrations of metoprolol were shown to be were 4.9-fold higher in the PMs, with greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in...

The wild type (normal) allele at this SNP is (C). The (T) variant indicates the presence of a non-wild type CYP2D6 variant, but it appears in many different variants so it can not be used to determine the presence of any particular variant. The most common variants it appears in are CYP2D6*10 and CYP2D6*4, but these are not the only ones. While this is the defining mutation for CYP2D6*10, it is not possible by itself for this mutation to determine a particular variant. In addition, the CYP2D6*4 variant includes this mutation, but the defining mutation 1846G>A SNP is not available in the common direct to consumer testing services. While it is not possible for this mutation to identify one particular variant, all the variants in which it appears have reduced or no CYP2D6 activity. If two ...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs2234922, also known as His139Arg, is a SNP in the microsomal epoxide hydrolase EPHX1 gene. [PharmGKB:Curated Risk or phenotype-associated allele: G. Phenotype: In a logistic regression model adjusted for history of phenytoin use during the first trimester and maternal epilepsy, the maternal EPHX1 139 R (rs2234922A/G) allele was associated with craniofacial abnormalities in the child. Study size: 157 pregnancies. Study population/ethnicity: phenytoin use during the first trimester and maternal epilepsy. metric(s): per rare allele OR: 2.33, 95% CI: 1.09-5.00, P=0.03. Type of association: GN.] [OMIM:EPOXIDE HYDROLASE POLYMORPHISM]

[PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: The AA homozygote was associated with lower clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): Type of association: PK.]

A 2009 report concludes that SNPs in the TGFBR2 gene do not appear to affect risk of abdominal aortic aneurysm (AAA). [PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.0355 (ANOVA); p = 0.1156 (QMIS); p = 0.0830 (KW) Type of association: PK.]

[PharmGKB:Curated Risk or phenotype-associated allele: A Phenotype: The CHST3:rs12418 A variant was associated with positive clincial response (partial or complete response) to treatment. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.0005 Type of association: PD; CO]

[PharmGKB:Curated Risk or phenotype-associated allele: A Phenotype: The CHST3:rs1871450 A variant was associated with positive clincial response (partial or complete response) to treatment and toxicity to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.048 (response); p = 0.006 (TOX) Type of association: PD; CO; TOX]

[PharmGKB:Curated Risk or phenotype-associated allele: C Phenotype: The CHST3:rs4148945 C variant was associated with positive clincial response (partial or complete response) to treatment and toxicity to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.011 (response); p = 0.010 (TOX) Type of association: PD; CO; TOX]

[PharmGKB:Curated Risk or phenotype-associated allele: C Phenotype: The CHST3:rs4148947 C variant was associated with positive clincial response (partial or complete response) to treatment. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.0023 Type of association: PD; CO]

[PharmGKB:Curated Risk or phenotype-associated allele: A Phenotype: The CHST3:rs4148950 A variant was associated with positive clincial response (partial or complete response) to treatment and toxicity to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s):p = 0.024 (response); p = 0.006 (TOX) Type of association: PD; CO; TOX]

[PharmGKB:Curated Risk or phenotype-associated allele: A Phenotype: The CHST3:rs730720 A variant was associated with positive clincial response (partial or complete response) to treatment. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.0034 Type of association: PD; CO]

This SNP, in the GSTP1 gene influences asthma risk; the (A) allele encodes the Ile, while the (G) allele encodes the Val. This SNP is also known as GSTP1Val105, or GSTP1 Ile105Val. This research paper shows that 13- to 21-year-olds exposed to tobacco smoke at home, with this mutation had more severe asthma than those without the mutation. rs1695 is also mentioned in this bbc article Several papers published findings associating GSTP1 Ile105Val genotypes with bronchial, childhood, or atopic asthma. Note that some studies, however, have not observed any association between this SNP and asthma in certain populations , or even more paradoxically, have observed that rs1695(G;G) homozygotes appear to be somewhat protected (OR 0.29) from developing asthma compared to individuals with rs1695(A;G) ...

[PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.1013 (ANOVA); p = 0.0159 (QMIS); p = 0.0178 (KW) Type of association: PK.]

[PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.3743 (ANOVA); p = 0.6323 (QMIS); p < 0.000001 (KW) Type of association: PK.]

rs12762549 and rs11045585 can be used to predict whether docetaxel will induced leukopenia/neutropenia, according to a study of ~100 Japanese patients. When patients were classified into three groups by the scoring system based on the genotypes of these two SNPs, patients with a score of 1 or 2 were shown to have a significantly higher risk of docetaxel-induced leukopenia/neutropenia as compared to those with a score of 0 (P = 0.0000057; odds ratio [OR], 7.00; 95% CI [confidence interval], 2.95-16.59). This prediction system correctly classified 69.2% of severe leukopenia/neutropenia and 75.7% of non-leukopenia/neutropenia into the respective categories. [PharmGKB:Curated In a case control study using samples from BioBank Japan, the G allele of rs12762549 was associated with docetaxel-ind...

[PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: The CYP4B1:rs4646487 T variant was associated with toxicity in response to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s):p = 0.008 Type of association: CO; TOX]

rs2228001, also known as Lys939Gln, K939Q, and K940Q, is a SNP in the DNA nuclear excision repair gene xeroderma pigmentosum complementation group C XPC gene. The Lys (K) allele is encoded by the rs2228001(A) allele. A meta-analysis of 16 studies with 6797 cancer cases and 9018 controls concluded that rs2228001(C;C) homozygotes had an increased overall cancer risk (odds ratio of 1.16, CI: 1.05-1.28) compared with (A;A) homozygotes. This was primarily a risk for lung cancer. [PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.0045 (ANOVA); p = 0.052 (QMIS); p = 0.0004 (KW) Type of association...

[PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.0097 (ANOVA); p = 0.0013 (QMIS); p = 0.0040 (KW) Type of association: PK.]

[PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.1495 (ANOVA); p = 0.2805 (QMIS); p = 0.0126 (KW) Type of association: PK.]

[PharmGKB:Curated Risk or phenotype-associated allele: G Phenotype: The PPAR delta SNP rs1883322 A>G was associated with positive clincial response (partial or complete response) to treatment. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.0061 Type of association: PD; CO]

[PharmGKB:Curated Risk or phenotype-associated allele: G Phenotype: The ABCC6 rs2238472 G variant was associated with toxicity in response to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.006 Type of association: CO; TOX] [OMIM:PSEUDOXANTHOMA ELASTICUM]

[PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: The PPAR delta SNP rs3734254 C>T was associated with positive clincial response (partial or complete response) to treatment. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.0089 Type of association: PD; CO]

[PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: The SLC10A2:rs2301159 T variant was associated with toxicity in response to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.01 Type of association: CO; TOX]

[PharmGKB:Curated Risk or phenotype-associated allele: G Phenotype: The SPG7:rs12960 G variant was associated with toxicity in response to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.004 Type of association: CO; TOX]

[PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: The SPG7:rs2292954 T variant was associated with toxicity in response to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.0004 Type of association: CO; TOX]

rs12762549 and rs11045585 can be used to predict whether docetaxel will induce leukopenia/neutropenia, according to a study of ~100 Japanese patients. When patients were classified into three groups by the scoring system based on the genotypes of these two SNPs, patients with a score of 1 or 2 were shown to have a significantly higher risk of docetaxel-induced leukopenia/neutropenia as compared to those with a score of 0 (P = 0.0000057; odds ratio [OR], 7.00; 95% CI [confidence interval], 2.95-16.59). This prediction system correctly classified 69.2% of severe leukopenia/neutropenia and 75.7% of non-leukopenia/neutropenia into the respective categories. [Effect percentages provided in table are raw population fractions taken from the referenced study based on rs11045585 only. Total populat...

[PharmGKB:Curated Risk or phenotype-associated allele: G Phenotype: The PPAR delta SNP rs6922548 A>G was associated with positive clincial response (partial or complete response) to treatment. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.0011 Type of association: PD; CO]

[PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: This variant was associated with higher clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): Type of association: PK.]

[PharmGKB:Curated Risk or phenotype-associated allele: C Phenotype: The CHST3:rs4148943 C variant was associated with positive clincial response (partial or complete response) to treatment. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.0001 Type of association: PD; CO]

[PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: This variant was associated with higher clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): Type of association: PK.]

[PharmGKB:Curated Risk or phenotype-associated allele: G Phenotype: The SULT1C2: rs1402467 G variant was associated with positive clincial response (partial or complete response) to treatment. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.0083 Type of association: PD; CO]

[PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.0043 (ANOVA); p = 0.0261 (QMIS); p = 0.0622 (KW) Type of association: PK.]

[PharmGKB:Curated Risk or phenotype-associated allele: G Phenotype: The ATP7A:rs2227291 G variant was associated with toxicity in response to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.006 Type of association: CO; TOX]

[PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.0045 (ANOVA); p = 0.052 (QMIS); p = 0.0004 (KW) Type of association: PK.]

[PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.0998 (ANOVA); p = 0.2400 (QMIS); p = 0.0021 (KW) Type of association: PK.]

[PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.0114 (ANOVA); p = 0.0341 (QMIS); p = 0.0294 (KW) Type of association: PK.]

[PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.0203 (ANOVA); p = 0.0552 (QMIS); p = 0.0003 (KW) Type of association: PK.]

rs1056836, also known as 4326C/G, Val432Leu or L432V, is a SNP in the cytochrome P450 1B1 (CYP1B1) gene. This gene is a member of the CYP1 gene family and one of the major enzymes involved in the hydroxylation of estrogens, a reaction likely to be relevant in hormonal carcinogenesis. [In dbSNP orientation, the (C) allele encodes the Leu; the (G) the Val.] In a study of 153 Hispanic Caucasians with prostate cancer the rs1056836(G;G) genotype showed decreased risk compared to the more common (C;C) genotype (odds ratio = 0.31, p = 0.04, CI: 0.10-0.96). This report cites another study as indicating that rs1056836(C;C) high-risk stage III and IV breast cancer patients receiving dose-intense paclitaxel in combination with doxorubicin and cyclophosphamide experience a longer progression-free surv...

Associated with baseline cholesterol levels in a study of 9,000+ individuals in Washington County, Maryland. [PharmGKB:Curated Risk or phenotype-associated allele: G Phenotype: The PPAR delta SNP rs2016520 A>G was associated with positive clincial response (partial or complete response) to treatment. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.0056 Type of association: PD; CO]

rs1799931 is a SNP in the NAT2 gene, potentially encoding a variant detoxifying protein known as an N-acetyltransferase, but which NAT2 variant depends on which other NAT2 SNPs were also inherited. See the discussion of the NAT2 gene for a more complete explanation. The risk allele for this SNP is rs1799931(A). [PharmGKB:Curated Risk or phenotype-associated allele: G Phenotype: The NAT2:rs1799931 G variant was associated with toxicity in response to docetaxel and thalidomide. Study size: 47 Study population/ethnicity: Patients diagnosed with castration-resistant prostate cancer enrolled in a randomized phase II clinical trial comparing docetaxel to docetaxel with thalidomide. Significance metric(s): p = 0.003 Type of association: CO; TOX] [OMIM:?]

[PharmGKB:Curated Risk or phenotype-associated allele: Not specified. Phenotype: This SNP was associated with clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): p = 0.0240 (ANOVA); p = 0.0084 (QMIS); p = 0.0534 (KW) Type of association: PK.]

The rs2740574(G) allele encodes a variant form of CYP3A4 known as CYP3A4*1B. rs2740574(G) alleles are associated with an ~10 fold higher risk of aggressive prostate cancer in African American males. [PMID 16414488, OMIM A pooled study (1,400+ samples) along with a replication study conducted by members of the Ovarian Cancer Association Consortium found a 2.5-2.8x increased risk for ovarian cancer] for rs2740574(G;G) individuals (CI: 1.2-6.5, p=0.017). The authors note that CYP3A4 encodes a key enzyme in estrogen metabolism and which may be linked to ovarian carcinogenesis. [PharmGKB:Curated Risk or phenotype-associated allele: CYP3A4*1B, rs2740574 G allele. Phenotype: CYP3A4*1B (rs2740574 G) allele carriers show a significantly increased risk for SCLC (OR = 2.25, p = 0.02), which showed a...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

The minor allele (G) of rs25531 is almost always in phase with the long (L) allele of the 5-HTTLPR, which is the most commonly studied variation in this region. The (L) long allele may be associated with lower levels of serotonin. The article and video from 'The Atlantic' suggests that children with the short allele (A), may need and benefit greatly from more maternal support *http://www.theatlantic.com/doc/200912/dobbs-orchid-gene In contrast to earlier reports linking rs25531, a SNP in the serotonin transporter SLC6A4 gene, to obsessive compulsive disorder (OCD), a March 2007 publication finds no significant association studying 'the largest sample size of OCD patients (N=347) and controls (N=749) ever investigated'. A separate study of 75 patients suffering mood disorders after traumati...

escitalopram response [GWAS:Response to antidepressants]

[PharmGKB:Curated This variant is associated with response to escitalopram and nortriptyline in a study of 760 adult patients with moderate-to-severe depression.]

[PharmGKB:Curated This variant is associated with response to escitalopram and nortriptyline in a study of 760 adult patients with moderate-to-severe depression.]

[PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: The CYP2C19*17 allele was associated with significantly increased metabolism of imipramine. Study size: 178 Study population/ethnicity: Psychiatric patients aged 18-65 with a score of greater than or equal to 17 on the Hamilton Rating Scale for Depression. Significance metric(s): p = 0.035 Type of association: PK]

[PharmGKB:Curated A sudy of 760 adult patients with moderate-to-severe depression, treated with escitalopram found that individuals carrying two minor alleles of rs9316233 variant in the HTR2A gene achieved an improvement that was on average 3.1 MADRS points more than individuals carrying two common alleles during escitalopram treatment. This explains 1.1% of variance (P=0.0016) of the response to escitalopram.]

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. A study of 1,000+ breast cancer patients showed a 0.77x decreased risk of breast cancer for carriers of a CYP2C19*17 allele (CI: 0.65-0.93, p = 0.005). Analysis of a subgroup of such carriers who were using hormone therapy for ten years or longer showed an even stronger effect (odds ratio 0.57, CI: 0.39-0.83, p = 0....

rs28399504 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*4 variant. This variant has been linked to poor metabolism of compounds like mephenytoin. It is also known as M1V or Met1Val. The risk allele is rs28399504(G). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). According to a 23andMe discussion This is one of the SNPs which were re-analyzed April 2009. Customers with older data may wish to redownload. SNPs effected rs4420638, rs34276300, rs3091244, rs34601266, rs2033003, rs7900194, rs9332239, rs28371685, rs1229984, and rs28399504. [PharmGKB:Curated Subjects ...

rs4244285 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*2 variant. This variant is the most common reason for poor metabolism of compounds like mephenytoin (an anti-convulsant), some antidepressants, the anti-platelet drug Plavix, and some drugs used for ulcer conditions of various types. The risk allele is rs4244285(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (trade name Prevacid). In Caucasians, SNPs in CYP2C19 are relatively rare (in contrast to SNPs in CYP2D6), but SNPs in this gene are common in Asians. Ulcer treatment with omeprazole to reduce Helicobacter pyl...

rs4986893 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*3 variant. This variant has been linked to poor metabolism of compounds like mephenytoin as well as proguanil, and it therefore has implications for malaria prophylaxis. The risk allele is rs4986893(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). [PharmGKB:Curated In contrast to other PPIs, esomeprazole-induced healing of GERD appears to be unrelated to the CYP2C19*3 variant.] [OMIM:MEPHENYTOIN, POOR METABOLISM OF]

[PharmGKB:Curated system: membrane vessicles from HEK cells transfected with WT or variant; FA: variant had approx 50% decrease in transport of tritium labelled 17[beta]-estradiol-17[beta]-D-glucuronide (17E2b-g) due to decrease in Km]

[PharmGKB:Curated Risk or phenotype-associated allele: 2012GT (671Gly/Val) genotype. Phenotype: Carriers the heterozygous 2012GT (671Gly/Val) genotype had lower serum HDL cholesterol than the GG (671Gly/Gly) genotype carriers (p = 0.015). Study size: 136. Study population/ethnicity: Hypercholesterolemic individuals, treated with atorvastatin (10mg/day/4 weeks), evaluated for CAD risk factors at the Institute Dante Pazzanese of Cardiology and the Hospital of the Sao Paulo University in Sao Paulo City, Brazil. Significance metric(s): p = 0.015. Type of association: GN; PD; FA]

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

This SNP in the GABRA2 gene has been linked to Alcoholism. The effect of this SNP, a synonymous change at amino acid residue 132, is unknown, but it does not change the GABRA2 protein sequence. Carriers of at least one rs279858(G) allele respond slower to the effects of alcohol and are thereby apparently more prone to alcoholism than carriers of two rs279858(A) alleles. Finasteride, an FDA approved drug for the treatment of benign prostatic hypertrophy and a modulator of GABRA2, was shown to have more of a blocking effect on rs279858(A) homozygotes. Note that nearby SNPs have been grouped into a haplotype that shows statistically stronger association with alcohol dependence, namely the haplotype consisting of the rs279871(A) + rs279845(T) + rs279836(A) alleles . 1050 nicotine-dependent cas...

rs2395029 is a SNP in the major histocompatibility complex (MHC) region, and several studies have shown that the rs2395029(G) allele is 99.9% predictive of the presence of an HLA-B*5701 allele. This HLA allele, in turn, has been associated with several conditions. A study of 51 cases of flucloxacillin drug-induced liver injury (DILI), an important cause of serious liver disease, along with a replication study of another 23 cases, found that the rs2395029(G) carriers were at highly increased risk (odds ratio 80, p=8.7x10(-33)). * see also: spittoon rs2395029(G;G) increases the odds of drug-induced liver injury in response to flucloxacillin by 45x This SNP is thought to be involved in determining the HIV viral load set point during the asymptomatic period of infection. This SNP is estimated ...

In HLA-B*5701 carrier cases, i.e. rs2395029(G) carriers, rs10937275 showed an increased in risk for drug-induced liver injury for patients taking flucloxacillin. The odds ratio was 4.1 (p = 1.4 x 10(-8)). [PharmGKB:Curated This intronic variant of ST6GAL1 was significantly associated with flucloxacillin-induced liver injury in a GWAS screen (OR = 4.1, P = 1.4x10-8).] [OMIM:HLA COMPLEX P5 GENE; HCP5]

rs1042713, also known as Arg16, G16R, and 16Arg>Gly, is a SNP in the adrenergic, beta-2-, surface receptor ADRB2 gene. The rs1042713(G) allele encodes the G/glycine form that is the more common one in most populations, while rs1042713(A) encodes the R/arginine residue at this position of the ADRB2 protein. A study of 1,182 young Scottish asthma patients (age, 3-22 years) concluded that rs1042713(A) alleles are significantly associated with 'exacerbations' of their condition, regardless of treatment regimens (odds ratio 1.30, CI: 1.09-1.55, p=0.003). This didn't hold true for patients using inhalers less than once per day; and it was particularly true for those receiving daily inhaled long- or short-acting beta(2)-agonist treatment (OR, 1.64, CI: 1.22-2.20, p=.001). This may therefore in...

rs242941 is a SNP in the corticotrophin-releasing hormone receptor 1 CRHR1 gene. (G;G) better response to inhaled corticosteroids fluticasone propionate and salmeterol in patients with COPD in a Korean study with 84 subjects. [PharmGKB:Curated Haplotype tagging SNP.]

associated with bronchodilator response among a sample of 209 children and their parents participating in the Childhood Asthma Management Program, the minor allele was associated with lower BDR compared to the homozygous major allele [PharmGKB:Curated This variant is associated with acute response to inhaled ? agonists in both childhood and adult asthmatic patients.]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

[PharmGKB:Curated The T allele of -216G/T was associated with improved progression free survival in gefitinib-treated non-small-cell lung cancer patients. It was also associated with significantly higher rates of stable disease/partial response and a significantly higher risk of treatment-related rash/diarrhea.]

rs2293347, also known as D994D, is a SNP in the epidermal growth factor receptor EGFR gene. In a study of therapeutic outcome and survival in 84 advanced non-small-cell lung cancer (NSCLC) patients treated with Gefitinib, the response rate for rs2293347(G;G) patients was almost double that of other genotypes for this SNP (71.2% versus 37.5%, p=0.0043). The rs2293347(G;G) genotype was also associated with longer progression-free survival compared with the rs2293347(A;G) or (A;A) genotypes (11 months versus 3 months, p=0.0018).

rs2231142, also known as Q141K and C421A, is a SNP in the ABCG2 gene, indicating a missense variant. A is the risk allele. A large study totaling 7,699 participants in the Framingham cohort and 4,148 participants in the Rotterdam cohort was conducted, with genome-wide significant SNPs then replicated in 11,000+ Caucasian and ~4,000 African-American individuals who took part in the study of Atherosclerosis Risk in Communities (ARIC). This study calculated an odds ratio of 1.74 for rs2231142 (CI: 1.51-1.99, p = 3.3x10e-15). A genetic score comprised of this SNP plus 2 others may stratify risk for gout. Among non-small cell lung cancer patients treated with gefitinib, there's a 4-5x higher risk of diarrhea for rs2231142 heterozygotes (and presumably minor allele homozygotes), based on a study...

rs351855, a SNP in the fibroblast growth factor receptor 4 (FGFR4) gene, is also known as the Gly388Arg variant. The rs351855(T) allele encodes the risk (Arg) allele. The Arg form of this SNP is likely to cause a harder to treat version of node-positive breast cancer, including reducing the efficacy of Herceptin, based on a study of 372 patients. A study of ~500 Japanese prostate cancer patients found that individuals with a rs351855(T;T) genotype had a 2.2- and 1.9-fold increased risk of prostate cancer and benign prostate hyperplasia (BPH), and a 1.8-fold increased risk of metastatic prostate cancer compared to the (C;C) genotype. A meta-analysis published in 2011, surveying a total of 2,618 cases of prostate cancer, concluded that the odds ratio per rs351855(T) allele was 1.17 (CI: 1.07...

rs1136201 (Ile655Val) is a SNP within ERBB2/HER2 (Human epidermal growth factor receptor 2). (among 56 patients with breast cancer and 45 healthy women) Ile-Val and Val-Val genotypes exhibited highly significant serum HER-2 elevation compared to those homozygous for Ile-Ile among 61 patients with advanced breast cancers and treated by trastuzumab, all cases of cardiotoxicity occurred in the Ile-Val group and there was no cardiac toxicity in the Val-Val and Ile-Val patients, there was no link found between tumor response and survival w/ HER2 genotype [PharmGKB:Curated Risk or phenotype-associated allele: AC genotype (ERBB2 665 Ile/Val). Phenotype: Increased prevalence of breast cancer in individuals with the combined genotypes of ESR1 rs1801132 CC and ERBB2 665 Ile/Val (rs1136201 A/C). Stu...

[PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: The CYP2C19*17 allele was associated with significantly increased metabolism of imipramine. Study size: 178 Study population/ethnicity: Psychiatric patients aged 18-65 with a score of greater than or equal to 17 on the Hamilton Rating Scale for Depression. Significance metric(s): p = 0.035 Type of association: PK]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. A study of 1,000+ breast cancer patients showed a 0.77x decreased risk of breast cancer for carriers of a CYP2C19*17 allele (CI: 0.65-0.93, p = 0.005). Analysis of a subgroup of such carriers who were using hormone therapy for ten years or longer showed an even stronger effect (odds ratio 0.57, CI: 0.39-0.83, p = 0....

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

This SNP in the tumor necrosis factor-alpha gene, rs1800629, is also known as the TNF-308 SNP. Occasionally the rs1800629(A) allele is referred to as 308.2 or TNF2, with the more common (G) allele being 308.1 or TNF1. The (A) allele is associated with higher levels of TNF expression. This SNP has been linked to a wide variety of conditions: * Allograft rejection ** Among 72 Polish patients receiving a kidney transplant, the risk of acute kidney allograft rejection was 2.5x higher among rs1800629(A) carriers compared to (G;G) homozygotes (CI: 1.19- 5.37, p<.05). * Asthma ** A meta-analysis of ~2,500 patients combined indicated that the rs1800629(A) allele was associated with a 1.46x increased risk for asthma. ** In a study of ~600 Mexican families and their asthmatic children, rs1800629(...

rs3849942 is one of 2 SNPs from the ch 9p21.2 region associated in a large GWAS study with ALS risk, the other SNP being rs2814707. In this study, the reported odds ratio for rs3849942(A) was 1.22 (CI: 1.15 - 1.30, p = 4.64 x 10e-10). The odds ratio for the minor rs3849942(A) allele was 1.15 (p=1.01x10e-8). From a study of 405 Finnish patients with ALS, rs3849942 was found within a 42 SNP haplotype associated with highly increased (p = 7 x 10e-33) risk when patients with familial ALS were compared to controls (odds ratio of 21.0, CI: 11.2-39.1). This haplotype overlapped with a region reported (by others) to associate with risk for frontotemporal dementia. In terms of population attributable risk, for the 93 patients with familial ALS, this 9p21 locus accounts for 38% and that of rs1304801...

rs2814707 is one of 2 SNPs from the ch 9p21.2 region associated in a large GWAS study with ALS risk, the other SNP being rs3849942. In this study, the reported odds ratio for rs2814707(A) was 1.22 (CI: 1.15 - 1.30, p = 4.72 x 10e-10). The odds ratio for the minor rs2814707(A) allele was 1.16 (p=7.45x10e-9). spittoon rs2814707(T) 1.16x odds of ALS rs12608932(C) 1.2x odds of ALS [PharmGKB:Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000002; OR: 5.2 (1.8, 16.7)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.] [OMIM:?]

[PharmGKB:Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000006; OR: 5.4 (1.9, 17.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.] [GWAS:Amyotrophic lateral sclerosis]

[PharmGKB:Non-Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000005; OR: 4.9 (1.8, 14.0)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.] [GWAS:Treatment response to TNF antagonists]

[PharmGKB:Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000005; OR: 4.9 (1.8, 14.0)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.]

[PharmGKB:Curated For this SNP in the TNFRSF1B gene a significant correlation was found between 196R allele carriers and low response to infliximab therapy.]

rs1801274 is a SNP in the Fc fragment of IgG, low affinity IIa, receptor (CD32) FCGR2A gene. rs1801274(C) encodes the arginine (R) allele, with the (T) allele encoding the variant histidine (H). The (H) isoform is considered high-binding to IgG2 and IgG3, while the (R) isoform is considered low-binding. This SNP is known in the literature by many names, including A519C and R131H. What's the importance of this? FcgR isoforms expressed on immune system cells have been linked to the pathogenic consequences triggered by autoantibodies or immune complexes in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as well as to the efficacy of some immunotherapeutic treatments such as rituximab. Many studies have been published about this FCGR2A SNP, roughly...

[PharmGKB:Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000003; OR: 7.6 (1.9, 44.6)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.]

[PharmGKB:Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000002; OR: 11.2 (2.3, 108.1)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.] [GWAS:Treatment response to TNF antagonists]

[PharmGKB:Non-Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000004; OR: 4.6 (1.8, 12.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.] [GWAS:Treatment response to TNF antagonists]

[PharmGKB:Non-Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000002; OR: 4.6 (1.8, 12.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.] [GWAS:Treatment response to TNF antagonists]

[PharmGKB:Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000006; OR: 3.6 (1.5, 9.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.]

[PharmGKB:Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.00003; OR: 5.5 (1.8, 20.2)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.]

[PharmGKB:Non-Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.0000003; OR: 4.6 (1.8, 12.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.] [GWAS:Treatment response to TNF antagonists]

[PharmGKB:Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000003; OR: 8.5 (2.6, 36.5)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.]

[PharmGKB:Non-Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000005; OR: 10.2 (2.6, 59.2)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.] [GWAS:Treatment response to TNF antagonists]

[PharmGKB:Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000003; OR: 11.1 (2.5, 103.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.] [GWAS:Treatment response to TNF antagonists]

[PharmGKB:Curated This variant is significantly associated with the efficacy of anti-TNF treatment in rheumatoid arthritis (Adjusted P-value: 0.000004; OR: 6.8 (1.7, 40.3)). The study is a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning of anti-TNF therapy.] [GWAS:Treatment response to TNF antagonists]

rs2231142, also known as Q141K and C421A, is a SNP in the ABCG2 gene, indicating a missense variant. A is the risk allele. A large study totaling 7,699 participants in the Framingham cohort and 4,148 participants in the Rotterdam cohort was conducted, with genome-wide significant SNPs then replicated in 11,000+ Caucasian and ~4,000 African-American individuals who took part in the study of Atherosclerosis Risk in Communities (ARIC). This study calculated an odds ratio of 1.74 for rs2231142 (CI: 1.51-1.99, p = 3.3x10e-15). A genetic score comprised of this SNP plus 2 others may stratify risk for gout. Among non-small cell lung cancer patients treated with gefitinib, there's a 4-5x higher risk of diarrhea for rs2231142 heterozygotes (and presumably minor allele homozygotes), based on a study...

The (C;C) genotype is linked to reduced UGT1A1 activity, and increased Bilirubin, except in people of African origin for whom the T allele is a risk factor for breast cancer. [PharmGKB:Curated *60 is a common variant of UGT1A1. It is located in the Phenobarbital Response Enhancer Module (an upstream regulatory sequence) and may be involved in irinotecan response and in Gilbert syndrome.]

[PharmGKB:Curated The AUCs of irinotecan, SN-38, SN-38 glucuronide, and APC are influenced by rs3740066, rs2306283, rs35605, rs10276036, and rs717620 .]

[PharmGKB:Curated Risk or phenotype-associated allele: T. Phenotype: This SNP was associated with increased risk of myelosuppression in cancer patients treated with irinotecan. Study size: 108. Study population/ethnicity: Japanese patients with neoplasms; Japan. Significance metric(s): p = 0.036. Type of association: PK; CO.]

[PharmGKB:Non-Curated The AUCs of irinotecan, SN-38, SN-38 glucuronide, and APC are influenced by rs3740066, rs2306283, rs35605, rs10276036, and rs717620 .]

[PharmGKB:Non-Curated The AUCs of irinotecan, SN-38, SN-38 glucuronide, and APC are influenced by rs3740066, rs2306283, rs35605, rs10276036, and rs717620 .]

[PharmGKB:Curated UGT1A7:-57T>G increases risk of anemia in irinotecan-treated patients.]

Clinically relevant UGT1A10 variant. [PharmGKB:Curated *93 is a common variant of UGT1A1 in Caucasian and African-American populations. It is located in the Phenobarbital Response Enhancer Module (an upstream regulatory sequence) and may be important in predicting irinotecan response.]

[PharmGKB:Non-Curated ABCC2*2 (−1019a>G) is associated with lower irinotecan clearance and with significant reduction in severe diarrhea in cancer patients.]

rs34815109 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene. This gene encodes a protein that modifies hepatic bilirubin in order to allow it to be excreted. SNPs that reduce the activity of the UGT1A1 gene therefore tend to increase serum bilirubin levels. The rs34815109(TA) allele represents the insertion variant, which actually adds a seventh (TA) pair to what is already a string of six (TA) pairs; this reduces the activity to 30% of normal, and is thus the risk allele. The risk allele is commonly referred to as the UGT1A1*28 allele, and it is homozygous in ~10% of the US population. Risks associated with the rs34815109(TA) allele are almost always associated with the homozygous (TA;TA) genotype, with smaller (or no) effects...

rs34983651 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene; the primary entry in SNPedia for this set of SNPs is at rs34815109. The other two SNPs (besides rs34815109) that also describe the same polymorphism are: * rs35600288 * rs5839491

rs35600288 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene; the primary entry in SNPedia for this set of SNPs is at rs34815109. The other two SNPs (besides rs34815109) that also describe the same polymorphism are: * rs34983651 * rs5839491

rs5839491 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene; the primary entry in SNPedia for this set of SNPs is at rs34815109. The other two SNPs (besides rs34815109) that also describe the same polymorphism are: * rs35600288 * rs34983651

This SNP, a variant in the TP53 gene, is 1 of 25 SNPs reported to represent independently minor, but cumulatively significant, increased risk for breast cancer. For details of all 25 SNPs in this group, along with the two methods used to calculate overall risk estimates for breast cancer, refer to the SNPedia breast cancer entry. For this particular SNP, the risk (minor) allele is (C). The minor allele encodes an arginine at position 72 of the protein (where there's normally a proline), and the SNP is commonly called the Arg72 variant, although P72R and Arg72Pro are also common in the literature. Minor allele homozygotes, i.e. rs1042522(C;C) genotypes, live on average 3 years longer than major allele (G;G) homozygotes, based on a study of 9,200+ Danish individuals. The increased longevity ...

rs3740066, a SNP in the ABCC2 gene, is reported to be associated with a higher risk of developing intrahepatic cholestasis of pregnancy (ICP) based on a study of ~70 Argentinian patients. ICP is associated with increased fetal risks such as premature birth or intrauterine death. The risk allele is rs3740066(A), and the odds ratio for homozygous rs3740066(A;A) mothers is 4.44 (CI: 1.83 - 10.78), and for heterozygous mothers 1.65 (CI: 0.76 - 3.64), compared to rs3740066(G;G) mothers. [PharmGKB:Curated The AUCs of irinotecan, SN-38, SN-38 glucuronide, and APC are influenced by rs3740066, rs2306283, rs35605, rs10276036, and rs717620 .]

rs4148323, a SNP also known as 211G>A or G71R, occurs in the UGT1A1 gene, and defines the UGT1A1*6 allele. This allele is associated with Gilbert's syndrome among Asians, Crigler-Najjar syndrome type II (CN-II), and transient familial neonatal hyperbilirubinemia. rs4148323(A) in exon 1 of the UGT1A1 gene is associated with hyperbilirubinemia. rs4148323 and several other nearby SNPs help predict serum total bilirubin levels, based on a study of 750 Japanese. [PharmGKB:Curated *6 is the most common UGT1A1 coding variant found in Asians. It may result in reduced capacity to metabolize irinotecan and hence irinotecan toxicity.] [OMIM:UDP-GLYCOSYLTRANSFERASE 1 FAMILY, POLYPEPTIDE A1; UGT1A1]

rs4149056, also known as 37041T>C or V174A, is a SNP in the SLCO1B1 gene, which encodes the 'organic anion transporting polypeptide 1B1' (OATP1B1) protein. This protein, found primarily in the liver, regulates the uptake of numerous drugs and natural compounds. The rs4149056(C) SNP defines the SLCO1B1*5 allele. The rs4149056(C) allele gives rise to an amino acid change (from valine to alanine at residue 174) which has reduced uptake/transport activity. Therefore, drugs metabolized by OATP1B1 tend to build up to higher circulating concentrations than they would otherwise.. The drugs known (or in some cases, thought) to be transported less well by the variant OATP1B1 protein encoded by the rs4149056(C) allele include: *Several cholesterol lowering statins, generally leading to reduced inh...

rs58597806 (Asp256Asn/D256N) is a SNP within UGT1A9 (UDP glucuronosyltransferase 1 family, polypeptide A9). reduced propofol glucuronidation - considerably lowered glucuronidation of mycophenolic acid, 1-naphthol, and naringenin. may be at risk adverse effects w/ propofol and other UGT1A9 substrate administration essentially non-functional with regard to SN-38 (7-ethyl-10-hydroxycamptothecin) glucuronidation, an active metabolite of irinotecan [PharmGKB:Curated A study in 100 healthy Japanese volunteers showed that carriers of D256N may be at risk of suffering adverse effects of propofol and other substrates that are primarily metabolized by UGT1A9. In in vitro analyses the K(m) of wild-type and D256N for propofol glucuronidation were 111.2 and 43.6 microM, respectively. The V(max) of D25...

CYP2C8 SNP, defining the CYP2C8*3 allele (along with rs11572080). Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of NSAIDs that are CYP2C8 or CYP2C9 substrates, such as aceclofenac, celecoxib, diclofenac, ibuprofen, indomethazine, lornoxicam, meloxicam, naproxen, piroxicam, tenoxicam and valdecoxib. [PharmGKB:Curated Risk or phenotype-associated allele: G. Phenotype: In woman, the risk of acute myocardial infarction (AMI) tended to be higher for subjects carrying the CYP2C8*3*3 genotype versus *1*1 (OR = 1.9). The CYP2C8*3 variants are 416G>A (rs10509681) and 1196A>G (rs11572080). Tested in all subjects, the risk of AMI was also higher in individuals carrying the CYP2C8*3 allele (*3*3; *1*3 versus*1*1) [1.2 (1.0-1.5...

CYP2C8 SNP, defining the CYP2C8*3 allele (along with rs10509681). Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of NSAIDs that are CYP2C8 or CYP2C9 substrates, such as aceclofenac, celecoxib, diclofenac, ibuprofen, indomethazine, lornoxicam, meloxicam, naproxen, piroxicam, tenoxicam and valdecoxib. [PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: This variant was associated with increased risk for neurotoxicity with paclitaxel treatment. Study size: 132. Study population/ethnicity: Patients with Neoplasms receiving paclitaxel; Spain. Significance metric(s): HR = 1.54 (0.96-2.47); p = 0.072. Type of association: PK; TOX.]

rs1799853 is a SNP in the CYP2C9 gene. The rs1799853(T) allele encodes a variant amino acid, cysteine, which has been linked to poor metabolism of warfarin and thus sensitivity . The common nomenclature for this polymorphism is CYP2C9*2 (Cys amino acid, T allele; the SNP is also known as C430T or Cys144Arg). The effect of CYP2C9 variants on drug metabolism should not be predicted without also considering CYP2C9*3, defined as the common loss of function variant rs1057910(C) (NM_000771:c.430C>T, NP_000762:p.144R>C) [http://www.pharmgkb.org/search/annotatedGene/cyp2c9/. Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of nonsteroidal anti-inflammatory drugs (NSAIDs) that are CYP2C8 or CYP2C9 substrates, such as aceclofena...

SNP rs1057910(A), located in the cytochrome p450 CYP2C9 gene, most commonly encodes the amino acid isoleucine at position 359, and the resulting allele is also known as CYP2C9*1. rs1057910(C) encodes a leucine at this same position, and the resulting allele is called CYP2C9*3. This SNP is also known as Ile359Leu or A1075C. The effect of CYP2C9 variants on drug metabolism should not be predicted without also considering CYP2C9*2, defined as the common loss of function variant rs1799853(T) (NM_000771:c.430C>T, NP_000762:p.144R>C) Studies of the effects of these alleles include: * rs1057910(C;C)] genotypes may clear drugs like celecoxib (trade name Celebrex) twice as slowly as rs1057910(A;A) genotypes; the rs1057910(A;C) genotypes are in-between clearance rates. Lower clearance rates wi...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

rs1045642, also known as C3435T, is a SNP located in the ABCB1 gene. It is often studied in conjunction with rs2032582. C3435T has been mentioned by: * A 'Silent' Polymorphism in the MDR1 Gene Changes Substrate Specificity (for example, to verapamil) * (R)-lansoprazole (Prevacid) concentrations are significantly increased in CYP2C19 extensive metabolizers with ABCB1 C3435T C allele. * In a Korean population, plasma concentrations of fexofenadine (Allegra) were 17% lower in 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects compared to 2677GG/3435CC subjects. * In contrast, in this study no association was observed between the C3435T polymorphism and fexofenadine plasma or urine concentrations in a German Caucasian population. * A meta-analysis including 9 case-control stud...

rs28399504 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*4 variant. This variant has been linked to poor metabolism of compounds like mephenytoin. It is also known as M1V or Met1Val. The risk allele is rs28399504(G). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). According to a 23andMe discussion This is one of the SNPs which were re-analyzed April 2009. Customers with older data may wish to redownload. SNPs effected rs4420638, rs34276300, rs3091244, rs34601266, rs2033003, rs7900194, rs9332239, rs28371685, rs1229984, and rs28399504. [PharmGKB:Curated Subjects ...

rs4244285 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*2 variant. This variant is the most common reason for poor metabolism of compounds like mephenytoin (an anti-convulsant), some antidepressants, the anti-platelet drug Plavix, and some drugs used for ulcer conditions of various types. The risk allele is rs4244285(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (trade name Prevacid). In Caucasians, SNPs in CYP2C19 are relatively rare (in contrast to SNPs in CYP2D6), but SNPs in this gene are common in Asians. Ulcer treatment with omeprazole to reduce Helicobacter pyl...

rs4986893 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*3 variant. This variant has been linked to poor metabolism of compounds like mephenytoin as well as proguanil, and it therefore has implications for malaria prophylaxis. The risk allele is rs4986893(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). [PharmGKB:Curated In contrast to other PPIs, esomeprazole-induced healing of GERD appears to be unrelated to the CYP2C19*3 variant.] [OMIM:MEPHENYTOIN, POOR METABOLISM OF]

rs2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r² >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are know...

rs28399504 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*4 variant. This variant has been linked to poor metabolism of compounds like mephenytoin. It is also known as M1V or Met1Val. The risk allele is rs28399504(G). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). According to a 23andMe discussion This is one of the SNPs which were re-analyzed April 2009. Customers with older data may wish to redownload. SNPs effected rs4420638, rs34276300, rs3091244, rs34601266, rs2033003, rs7900194, rs9332239, rs28371685, rs1229984, and rs28399504. [PharmGKB:Curated Subjects ...

rs4244285 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*2 variant. This variant is the most common reason for poor metabolism of compounds like mephenytoin (an anti-convulsant), some antidepressants, the anti-platelet drug Plavix, and some drugs used for ulcer conditions of various types. The risk allele is rs4244285(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (trade name Prevacid). In Caucasians, SNPs in CYP2C19 are relatively rare (in contrast to SNPs in CYP2D6), but SNPs in this gene are common in Asians. Ulcer treatment with omeprazole to reduce Helicobacter pyl...

rs4986893 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*3 variant. This variant has been linked to poor metabolism of compounds like mephenytoin as well as proguanil, and it therefore has implications for malaria prophylaxis. The risk allele is rs4986893(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). [PharmGKB:Curated In contrast to other PPIs, esomeprazole-induced healing of GERD appears to be unrelated to the CYP2C19*3 variant.] [OMIM:MEPHENYTOIN, POOR METABOLISM OF]

rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C). An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk. This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD). *rs20455, in the KIF6 gene *rs3900940, in the MYH15 gene *rs7439293, in the PALLD gene *rs2298566, in the SNX19 gene *rs1010, in the VAMP8 gene For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 pos...

rs1057868, also known as A503V, is a relatively common variant defining the POR*28 allele of the P450 (cytochrome) oxidoreductase POR gene. The POR gene encodes a protein involved in electron transport of cytochrome p450 enzymes such as CYP3A4, CYP3A5 and CYP3A7. A study of 251 individuals from two independent studies (182 patients treated with methadone and 69 patients with clozapine) for CYP3A activity found that CYP3A SNPs themselves did not predict particularly well inter-individual variability in overall CYP3A activity. However, rs1057868(T;T) individuals had a 1.6x increased CYP3A activity compared to rs1057868(C) carriers (n=182, p=0.004), and the finding was replicated in a second independent dataset. The authors conclude that this POR gene SNP is a better predictor of overall CYP3...

rs1128503 is a SNP in the transporter P-glycoprotein (P-gp) 170, encoded by the ABCB1 (also known as MDR1) gene. Methadone is a substrate of this protein, so variants may affect the efficacy and optimal dosage of this drug as used for treating opiate dependence. A study of 98 methadone-maintaining patients concluded that the higher (>150 mg/day) and lower (< or =150 mg/day) methadone dose groups differed significantly in their rs1128503 status (experiment-wise p = 0.0325). Furthermore, individuals with the 3-locus genotype pattern (T;T)-(T;T)-(T;T) for SNPs rs1045642, rs2032582 and rs1128503, respectively, had an approximately 5-fold chance of requiring the 'higher' methadone dose, while individuals heterozygous for these three SNPs have an approximately 3-fold chance of stabilizing ...

rs1045642, also known as C3435T, is a SNP located in the ABCB1 gene. It is often studied in conjunction with rs2032582. C3435T has been mentioned by: * A 'Silent' Polymorphism in the MDR1 Gene Changes Substrate Specificity (for example, to verapamil) * (R)-lansoprazole (Prevacid) concentrations are significantly increased in CYP2C19 extensive metabolizers with ABCB1 C3435T C allele. * In a Korean population, plasma concentrations of fexofenadine (Allegra) were 17% lower in 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects compared to 2677GG/3435CC subjects. * In contrast, in this study no association was observed between the C3435T polymorphism and fexofenadine plasma or urine concentrations in a German Caucasian population. * A meta-analysis including 9 case-control stud...

rs6275/DRD2 and rs4680/COMT useful in predicting disease risk among schizophrenia patients See also rs6277. [PharmGKB:Curated Risk or phenotype-associated allele: T. Phenotype: The average and maximum daily methadone doses were significantly associated with the DRD2 rs6275C>T SNP (P=0.016 and 0.005 for average and maximum dose, respectively). Carriers of the variant rs6275T allele needed higher methadone doses than noncarriers. Study size: 85. Study population/ethnicity: Caucasian. Type of association: GN.]

[PharmGKB:Curated Risk or phenotype-associated genotype: AA. Phenotype: The average methadone dose during the first year of substitution therapy were significantly larger in AA carriers (n=4) than in the other rs2070995 genotypes (p=0.003). Study Size: 85. Study population: Caucasian.]

rs6277 (957C>T, Pro319Pro) is one of several SNPs in the dopamine receptor DRD2 gene. In a study of 300+ Russian patients with schizophrenia, the rs6277(C) allele was associated with higher risk. From a pooled meta-study (total of 4 other reports plus this one) the allelic odds ratio is 1.42 (CI: 1.26-1.61, p<0.00005), and the genotypic odds ratio for the (C;C) genotype was 1.6 (CI: 1.32-1.95, p<0.00005). Note that rs6275 and rs6277 are only 18bp apart, hence their very tight linkage (r²=1). C allele associated significantly (p = 0.021) with post-traumatic stress disorder in a sample of (assumedly Australian) 127 war veterans w/ 228 controls spittoon people with two As at rs6277(T;T) were better at NoGo learning. [pharmgkb] T allele associated with decrease ...

The (-) form of this SNP, representing a deletion of one nucleotide, causes a frameshift such that the resulting CYP2D6 protein is nonfunctional. The associated allele is also known as CYP2D6*6, and there are several subtypes but they are all nonfunctional. If two copies of this (or similar) changes are inherited, CYP2D6 poor metabolism ('PM') is observed. CYP2D6 poor metabolism may affect the efficacy or degree of side effects of drugs metabolized by CYP2D6, such as dextromorphan, sparteine, nortriptyline, venlafaxine and codeine. [PharmGKB:Curated This variant is part of the CYP2D6*6 PM haplotype. Plasma concentrations of metoprolol were shown to be were 4.9-fold higher in the PMs, with greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in...

The wild type (normal) allele at this SNP is (C). The (T) variant indicates the presence of a non-wild type CYP2D6 variant, but it appears in many different variants so it can not be used to determine the presence of any particular variant. The most common variants it appears in are CYP2D6*10 and CYP2D6*4, but these are not the only ones. While this is the defining mutation for CYP2D6*10, it is not possible by itself for this mutation to determine a particular variant. In addition, the CYP2D6*4 variant includes this mutation, but the defining mutation 1846G>A SNP is not available in the common direct to consumer testing services. While it is not possible for this mutation to identify one particular variant, all the variants in which it appears have reduced or no CYP2D6 activity. If two ...

Variation at this SNP, located in the ADRB1 gene, may encode either the amino acid serine or glycine at amino acid position 49 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Ser49Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801253, which encodes an amino acid variant at position 389 of the same (ADRB1) protein. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized for patients with the corresponding genotypes as follows : *rs1801252(A...

rs28371725, also known as 2988G>A, is a SNP in the CYP2D6 gene. The rs28371725(A) allele defines the CYP2D6*41 variant, which has decreased activity. 23andMe also has SNP i4001476 at the same position. [PharmGKB:In-Depth This variant is part of the CYP2D6*41 IM haplotype. Plasma concentrations of metoprolol were shown to be were 4.9-fold higher in the PMs, with greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in non-PMs.]

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized f...

rs4680 (Val158Met) is a well studied SNP in the COMT gene. spittoon summarizes them as *rs4680(A) = Met, more exploratory, lower enzymatic activity *rs4680(G) = Val, less exploratory, higher enzymatic activity Roughly speaking, the predominant wisdom (known colloquially as the warrior/worrier hypothesis) posits that people with Val alleles have increased COMT activity and lower prefrontal extracellular dopamine compared with those with the Met substitution. Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergi...

rs4680 (Val158Met) is a well studied SNP in the COMT gene. spittoon summarizes them as *rs4680(A) = Met, more exploratory, lower enzymatic activity *rs4680(G) = Val, less exploratory, higher enzymatic activity Roughly speaking, the predominant wisdom (known colloquially as the warrior/worrier hypothesis) posits that people with Val alleles have increased COMT activity and lower prefrontal extracellular dopamine compared with those with the Met substitution. Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergi...

[PharmGKB:Curated Risk or phenotype-associated genotype: AA. Phenotype: The average methadone dose during the first year of substitution therapy were significantly larger in AA carriers (n=4) than in the other rs2070995 genotypes (p=0.003). Study Size: 85. Study population: Caucasian.]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

[PharmGKB:In-Depth This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.]

The rs1799971(G) allele in exon 1 of the mu opiod receptor OPRM1 gene causes the normal amino acid at residue 40, asparagine (Asn), to be replaced by aspartic acid (Asp). In the literature this SNP is also known as A118G, N40D, or Asn40Asp. Carriers of at least one rs1799971(G) allele appear to have stronger cravings for alcohol than carriers of two rs1799971(A) alleles, and are thus hypothesized to be more at higher risk for alcoholism. However, subsequent research results are mixed, and there are other studies both agreeing or disagreeing with this finding Among 200+ alcoholics treated with naltrexone, rs1799971(G) carriers receiving the drug (even without behavioral intervention) had an increased percentage of days abstinent (p = .07) and a decreased percentage of heavy drinking days (p...

The rs1799971(G) allele in exon 1 of the mu opiod receptor OPRM1 gene causes the normal amino acid at residue 40, asparagine (Asn), to be replaced by aspartic acid (Asp). In the literature this SNP is also known as A118G, N40D, or Asn40Asp. Carriers of at least one rs1799971(G) allele appear to have stronger cravings for alcohol than carriers of two rs1799971(A) alleles, and are thus hypothesized to be more at higher risk for alcoholism. However, subsequent research results are mixed, and there are other studies both agreeing or disagreeing with this finding Among 200+ alcoholics treated with naltrexone, rs1799971(G) carriers receiving the drug (even without behavioral intervention) had an increased percentage of days abstinent (p = .07) and a decreased percentage of heavy drinking days (p...

CYP2C8 SNP, defining the CYP2C8*3 allele (along with rs11572080). Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of NSAIDs that are CYP2C8 or CYP2C9 substrates, such as aceclofenac, celecoxib, diclofenac, ibuprofen, indomethazine, lornoxicam, meloxicam, naproxen, piroxicam, tenoxicam and valdecoxib. [PharmGKB:Curated Risk or phenotype-associated allele: G. Phenotype: In woman, the risk of acute myocardial infarction (AMI) tended to be higher for subjects carrying the CYP2C8*3*3 genotype versus *1*1 (OR = 1.9). The CYP2C8*3 variants are 416G>A (rs10509681) and 1196A>G (rs11572080). Tested in all subjects, the risk of AMI was also higher in individuals carrying the CYP2C8*3 allele (*3*3; *1*3 versus*1*1) [1.2 (1.0-1.5...

CYP2C8 SNP, defining the CYP2C8*3 allele (along with rs10509681). Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of NSAIDs that are CYP2C8 or CYP2C9 substrates, such as aceclofenac, celecoxib, diclofenac, ibuprofen, indomethazine, lornoxicam, meloxicam, naproxen, piroxicam, tenoxicam and valdecoxib. [PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: This variant was associated with increased risk for neurotoxicity with paclitaxel treatment. Study size: 132. Study population/ethnicity: Patients with Neoplasms receiving paclitaxel; Spain. Significance metric(s): HR = 1.54 (0.96-2.47); p = 0.072. Type of association: PK; TOX.]

rs1799853 is a SNP in the CYP2C9 gene. The rs1799853(T) allele encodes a variant amino acid, cysteine, which has been linked to poor metabolism of warfarin and thus sensitivity . The common nomenclature for this polymorphism is CYP2C9*2 (Cys amino acid, T allele; the SNP is also known as C430T or Cys144Arg). The effect of CYP2C9 variants on drug metabolism should not be predicted without also considering CYP2C9*3, defined as the common loss of function variant rs1057910(C) (NM_000771:c.430C>T, NP_000762:p.144R>C) [http://www.pharmgkb.org/search/annotatedGene/cyp2c9/. Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of nonsteroidal anti-inflammatory drugs (NSAIDs) that are CYP2C8 or CYP2C9 substrates, such as aceclofena...

SNP rs1057910(A), located in the cytochrome p450 CYP2C9 gene, most commonly encodes the amino acid isoleucine at position 359, and the resulting allele is also known as CYP2C9*1. rs1057910(C) encodes a leucine at this same position, and the resulting allele is called CYP2C9*3. This SNP is also known as Ile359Leu or A1075C. The effect of CYP2C9 variants on drug metabolism should not be predicted without also considering CYP2C9*2, defined as the common loss of function variant rs1799853(T) (NM_000771:c.430C>T, NP_000762:p.144R>C) Studies of the effects of these alleles include: * rs1057910(C;C)] genotypes may clear drugs like celecoxib (trade name Celebrex) twice as slowly as rs1057910(A;A) genotypes; the rs1057910(A;C) genotypes are in-between clearance rates. Lower clearance rates wi...

Variation at this SNP, located in the ADRB1 gene, may encode either the amino acid serine or glycine at amino acid position 49 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Ser49Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801253, which encodes an amino acid variant at position 389 of the same (ADRB1) protein. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized for patients with the corresponding genotypes as follows : *rs1801252(A...

Also known as Arg389, variation at this SNP, located in the ADRB1 gene, may encode either the amino acid glycine or arginine at amino acid position 389 of the corresponding protein, the beta-1 adrenergic receptor (hence why it is frequently called Arg389Gly). This protein is the target of beta blocker drugs, and so how well the drug works to help lower a patients high blood pressure depends in part on this SNP. The status of this SNP is often reported together with the status of SNP rs1801252, which encodes an amino acid variant at position 49 of the same (ADRB1) protein. The rs1801253(G) allele encodes the glycine. One of the best known studies of the effects of these 2 separate SNPs on the average efficacy of the beta blocker metoprolol in lowering blood pressure (BP) can be summarized f...

rs28399504 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*4 variant. This variant has been linked to poor metabolism of compounds like mephenytoin. It is also known as M1V or Met1Val. The risk allele is rs28399504(G). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). According to a 23andMe discussion This is one of the SNPs which were re-analyzed April 2009. Customers with older data may wish to redownload. SNPs effected rs4420638, rs34276300, rs3091244, rs34601266, rs2033003, rs7900194, rs9332239, rs28371685, rs1229984, and rs28399504. [PharmGKB:Curated Subjects ...

rs4244285 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*2 variant. This variant is the most common reason for poor metabolism of compounds like mephenytoin (an anti-convulsant), some antidepressants, the anti-platelet drug Plavix, and some drugs used for ulcer conditions of various types. The risk allele is rs4244285(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (trade name Prevacid). In Caucasians, SNPs in CYP2C19 are relatively rare (in contrast to SNPs in CYP2D6), but SNPs in this gene are common in Asians. Ulcer treatment with omeprazole to reduce Helicobacter pyl...

rs4986893 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*3 variant. This variant has been linked to poor metabolism of compounds like mephenytoin as well as proguanil, and it therefore has implications for malaria prophylaxis. The risk allele is rs4986893(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). [PharmGKB:Curated In contrast to other PPIs, esomeprazole-induced healing of GERD appears to be unrelated to the CYP2C19*3 variant.] [OMIM:MEPHENYTOIN, POOR METABOLISM OF]

rs1045642, also known as C3435T, is a SNP located in the ABCB1 gene. It is often studied in conjunction with rs2032582. C3435T has been mentioned by: * A 'Silent' Polymorphism in the MDR1 Gene Changes Substrate Specificity (for example, to verapamil) * (R)-lansoprazole (Prevacid) concentrations are significantly increased in CYP2C19 extensive metabolizers with ABCB1 C3435T C allele. * In a Korean population, plasma concentrations of fexofenadine (Allegra) were 17% lower in 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects compared to 2677GG/3435CC subjects. * In contrast, in this study no association was observed between the C3435T polymorphism and fexofenadine plasma or urine concentrations in a German Caucasian population. * A meta-analysis including 9 case-control stud...

[PharmGKB:Curated This variant is associated with response to escitalopram and nortriptyline in a study of 760 adult patients with moderate-to-severe depression.]

nortriptyline response [GWAS:Response to antidepressants]

[PharmGKB:Curated This variant is associated with response to escitalopram and nortriptyline in a study of 760 adult patients with moderate-to-severe depression.]

nortriptyline response [PharmGKB:Curated Risk or phenotype-associated allele: A Phenotype: The SNP within an intron of the uronyl 2-sulphotransferase gene was associated with outcome at a genome-wide level of significance and with a very small posterior probability of being a false positive. Carriers of the minor A allele experienced less improvement of depression symptoms than carriers of the GG homozygote from week 4 onward. Study size: 312 Study population/ethnicity: Individuals with unipolar depression of at least moderate severity treated with nortriptyline. Type of association: GN] [GWAS:Response to antidepressants]

The (-) form of this SNP, representing a deletion of one nucleotide, causes a frameshift such that the resulting CYP2D6 protein is nonfunctional. The associated allele is also known as CYP2D6*6, and there are several subtypes but they are all nonfunctional. If two copies of this (or similar) changes are inherited, CYP2D6 poor metabolism ('PM') is observed. CYP2D6 poor metabolism may affect the efficacy or degree of side effects of drugs metabolized by CYP2D6, such as dextromorphan, sparteine, nortriptyline, venlafaxine and codeine. [PharmGKB:Curated This variant is part of the CYP2D6*6 PM haplotype. Plasma concentrations of metoprolol were shown to be were 4.9-fold higher in the PMs, with greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in...

The wild type (normal) allele at this SNP is (C). The (T) variant indicates the presence of a non-wild type CYP2D6 variant, but it appears in many different variants so it can not be used to determine the presence of any particular variant. The most common variants it appears in are CYP2D6*10 and CYP2D6*4, but these are not the only ones. While this is the defining mutation for CYP2D6*10, it is not possible by itself for this mutation to determine a particular variant. In addition, the CYP2D6*4 variant includes this mutation, but the defining mutation 1846G>A SNP is not available in the common direct to consumer testing services. While it is not possible for this mutation to identify one particular variant, all the variants in which it appears have reduced or no CYP2D6 activity. If two ...

The normal (or wild type) form of this SNP is a (G). The (A) form disrupts proper mRNA formation, resulting in a nonfunctional CYP2D6 protein. The associated allele is also known as CYP2D6*4. The CYP2D6*4 allele is the most common nonfunctioning variant of CYP2D6. If two copies of this (or similar) changes are inherited, poor metabolism ('PM') of debrisoquine is observed. Many other drugs are typically first metabolized by CYP2D6 including dextromorphan, sparteine, metoprolol, nortriptyline and many other antidepressants and codeine. Of course, sometimes the active form of a drug is the one post-CYP2D6 metabolism; an example of this is tamoxifen, where the active form (endoxifen) is formed primarily via CYP2D6 metabolism; less functioning CYP2D6 can mean less benefit from taking the drug. ...

This SNP is associated with a higher risk of liver injury in patients taking the nonsteroidal anti-inflammatory drug lumiracoxib, which has been withdrawn from most markets.

People with one or two copies of the G allele at this SNP are 3.5 times more likely to suffer liver injury than TT carriers when taking the prescription nonsteroidal anti-inflammatory drug (NSAID) lumiracoxib. This new pain medication was approved in Europe in late 2006, but because of a higher incidence of liver injury and patient deaths than among patients using other NSAIDs, it was withdrawn from the market in most countries. It is still sold in some countries under the brand names Prexige and Joicela.

rs1799853 is a SNP in the CYP2C9 gene. The rs1799853(T) allele encodes a variant amino acid, cysteine, which has been linked to poor metabolism of warfarin and thus sensitivity . The common nomenclature for this polymorphism is CYP2C9*2 (Cys amino acid, T allele; the SNP is also known as C430T or Cys144Arg). The effect of CYP2C9 variants on drug metabolism should not be predicted without also considering CYP2C9*3, defined as the common loss of function variant rs1057910(C) (NM_000771:c.430C>T, NP_000762:p.144R>C) [http://www.pharmgkb.org/search/annotatedGene/cyp2c9/. Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of nonsteroidal anti-inflammatory drugs (NSAIDs) that are CYP2C8 or CYP2C9 substrates, such as aceclofena...

[PharmGKB:Curated Risk or phenotype-associated allele: T Phenotype: The CYP2C19*17 allele was associated with significantly increased metabolism of imipramine. Study size: 178 Study population/ethnicity: Psychiatric patients aged 18-65 with a score of greater than or equal to 17 on the Hamilton Rating Scale for Depression. Significance metric(s): p = 0.035 Type of association: PK]

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. A study of 1,000+ breast cancer patients showed a 0.77x decreased risk of breast cancer for carriers of a CYP2C19*17 allele (CI: 0.65-0.93, p = 0.005). Analysis of a subgroup of such carriers who were using hormone therapy for ten years or longer showed an even stronger effect (odds ratio 0.57, CI: 0.39-0.83, p = 0....

rs28399504 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*4 variant. This variant has been linked to poor metabolism of compounds like mephenytoin. It is also known as M1V or Met1Val. The risk allele is rs28399504(G). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). According to a 23andMe discussion This is one of the SNPs which were re-analyzed April 2009. Customers with older data may wish to redownload. SNPs effected rs4420638, rs34276300, rs3091244, rs34601266, rs2033003, rs7900194, rs9332239, rs28371685, rs1229984, and rs28399504. [PharmGKB:Curated Subjects ...

rs4244285 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*2 variant. This variant is the most common reason for poor metabolism of compounds like mephenytoin (an anti-convulsant), some antidepressants, the anti-platelet drug Plavix, and some drugs used for ulcer conditions of various types. The risk allele is rs4244285(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (trade name Prevacid). In Caucasians, SNPs in CYP2C19 are relatively rare (in contrast to SNPs in CYP2D6), but SNPs in this gene are common in Asians. Ulcer treatment with omeprazole to reduce Helicobacter pyl...

rs4986893 is a SNP in the CYP2C19 gene, potentially encoding the CYP2C19*3 variant. This variant has been linked to poor metabolism of compounds like mephenytoin as well as proguanil, and it therefore has implications for malaria prophylaxis. The risk allele is rs4986893(A). As a nonfunctioning CYP2C19, this variant would be expected to be a poor metabolizer of several commonly prescribed drugs, including anti-ulcer drugs like omeprazole (trade names Losec and Prilosec), esomeprazole (trade name Nexium), and lansoprazole (Prevacid). [PharmGKB:Curated In contrast to other PPIs, esomeprazole-induced healing of GERD appears to be unrelated to the CYP2C19*3 variant.] [OMIM:MEPHENYTOIN, POOR METABOLISM OF]

rs762551, also known as -164A>C or -163C>A, is a SNP encoding the CYP1A2*1F allele of the CYP1A2 gene. For historic reasons, the rs762551(C) allele is considered the wild-type, even though it is the rarer allele in most populations. The rs762551(A) allele is the 'fast metabolizer' allele known as CYP1A2*1F; the (C) allele is by comparison a slower metabolizer of certain substrates (including caffeine). In terms of genotypes, only rs762551(A;A) individuals are considered fast metabolizers. Individuals who are rs762551(A;C) heterozygotes or rs762551(C;C) homozygotes are both considered slow metabolizers. The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. One well known substrate of CYP1A2 is caffeine; individuals who are ca...

[PharmGKB:Curated Risk or phenotype-associated variant: G. Phenotype: The A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with atypical antipsychotic-induced obsessive compulsive symptoms. Study size: 94. Study population/ethnicity: Patients with schizophrenia receiving atypical antipsychotics; Asian; Korea. Significance metric(s): p = 0.04. Type of association: CO.]

[PharmGKB:Curated Risk or phenotype-associated variant: A. Phenotype: The A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with atypical antipsychotic-induced obsessive compulsive symptoms. Study size: 94. Study population/ethnicity: Patients with schizophrenia receiving atypical antipsychotics; Asian; Korea. Significance metric(s): p = 0.04. Type of association: CO.]

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 4 x 10^-7 for total cholesterol as a result of olanzapine use

rs1045642, also known as C3435T, is a SNP located in the ABCB1 gene. It is often studied in conjunction with rs2032582. C3435T has been mentioned by: * A 'Silent' Polymorphism in the MDR1 Gene Changes Substrate Specificity (for example, to verapamil) * (R)-lansoprazole (Prevacid) concentrations are significantly increased in CYP2C19 extensive metabolizers with ABCB1 C3435T C allele. * In a Korean population, plasma concentrations of fexofenadine (Allegra) were 17% lower in 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects compared to 2677GG/3435CC subjects. * In contrast, in this study no association was observed between the C3435T polymorphism and fexofenadine plasma or urine concentrations in a German Caucasian population. * A meta-analysis including 9 case-control stud...

rs6313, also known as T102C, is part of a 4-SNP haplotype in the serotonin 2A receptor gene HTR2A that has been associated with rheumatoid arthritis in a study of 1800 European patients. The risk allele is rs6313(C). The overall risk for the haplotype CTCC of SNPs rs6311-rs1328674-rs6313-rs6314 is 1.68 (CI: 1.20 - 2.34, p = 0.02). Note: the orientation of rs1328674 in dbSNP is opposite that cited by this publication; therefore, with respect to dbSNP, the haplotype of risk as cited above is CACC rather than CTCC. see also gs108 and gs226 Polymorphisms in the serotonin receptor gene HTR2A are associated with quantitative traits in panic disorder. [PharmGKB:Curated Risk or phenotype-associated allele (s): T/T. Phenotype: Patients, with a diagnosis of probable Alzheimer's disease, carryi...

[PharmGKB:Curated This intronic variant is moderately associated with olanzapine-induced median weight gain and significantly associated with extreme weight gain in schizophrenia subjects from north India.This variant alters the binding of a transcription factor (zinc finger 5) using in silico analysis.]

gwas, among 738 schizophrenics genotyped for 492K SNPs, this SNP attained a p-val of 3 x 10^-7 for total cholesterol as a result of olanzapine use

The ancestral allele is C. The rs7412(T) allele, also known as Arg176Cys, generally indicates the presence of an ApoE2 allele; see the ApoE page for a full discussion of the ApoE alleles and their association with Alzheimer's disease. Another SNP related to ApoE is rs429358. In a study of 67 mostly Caucasian patients prescribed the atypical antipsychotic olanzapine, carriers of a rs7412(C) allele were more likely to gain significant weight compared to rs7412(T;T) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, rs5092 and rs4765623, were also significantly associated with weight profiles in these patients. [PharmGKB:Curated Risk or phenotype-associated allele: The ApoE E2 allele is a combination of rs429358 T (130Cys) and rs7412 T (176Cys)....

[PharmGKB:Curated Risk or phenotype-associated allele: C. Phenotype: The C allele was associated with weight gain of at least 7% in schizophrenia patients treatment with clozapine or olanzapine. Study size: 206. Study population/ethnicity: European american; African American; German; Schizophrenia. Significance metric(s): OR = 3.44 (CI: 1.46-8.11). Type of association: PD.]

rs1799732 is a SNP in the D2 dopamine receptor gene DRD2 gene. Although dbSNP indicates the alleles as (C) or (-) (i.e. a deletion), investigators report the alleles as (C) or (T). In a study of individuals in the Polyp Prevention Trial with any, multiple (>/=2) or advanced colorectal adenoma recurrence after 4 years, compared to those without adenoma recurrence, rs1799732(C;T) individuals were significantly associated with all adenoma recurrence (odds ratio 1.30, CI: 1.01-1.69). The authors speculate this increased risk of adenoma recurrence (and an association with colorectal cancer) may be related to SNP-associated differences in alcohol and fat intake. spittoon Alcoholism related *rs1799971(A;A) severe alcoholism 2x *rs1799732(I;I) severe alcoholism 1.85x [PharmGKB:Curated Risk or ...

rs3813929, also known as -759C/T, is a SNP in the 5-hydroxytryptamine (serotonin) receptor 2C HTR2C gene. A study of 107 patients with schizophrenia being treated with olanzapine reported a protective effect against weight-gain from the (T) allele of this SNP; zero patients (of 28) with a rs3813929(T) allele had a body mass index increase of >=10% (p=0.002), whereas (C;C) homozygotes did. This effect may also involve nearby SNP rs518147. T allele showed borderline significant association with higher BMI and incidence of lifetime major depressive disorder among 4978 persons from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, however, only the association with BMI remained borderline significant within the full EPIC-Norfolk cohort (20,981 persons) [PharmGKB:Cura...

rs5092 is a SNP in the apolipoprotein A4 APOA4 gene. In a study of 67 mostly Caucasian patients prescribed the atypical antipsychotic olanzapine, carriers of a rs5092(G) allele were less likely to gain significant weight compared to rs5092(A;A) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, rs4765623 and rs7412, were also significantly associated with weight profiles in these patients.

rs7997012, located in an intron of the HTR2A gene, was found to be associated with a somewhat increased rate of successful response to treatment of depression with the drug citalopram. From this article : 'HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram. Participants who were homozygous for the A allele had an 18% reduction in absolute risk of having no response to treatment, compared with those homozygous for the other allele.' * See also Anxiety Blog posting [PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: Patients with the 5-HTR2A intron 2 (rs7997012) AA genotype suffered from more pronounced side effects compared to carriers of the GA or GG genotype. Study size: 124. Study population/ethnicity: Caucasian; Patients with psychiatric diso...

rs6277 (957C>T, Pro319Pro) is one of several SNPs in the dopamine receptor DRD2 gene. In a study of 300+ Russian patients with schizophrenia, the rs6277(C) allele was associated with higher risk. From a pooled meta-study (total of 4 other reports plus this one) the allelic odds ratio is 1.42 (CI: 1.26-1.61, p<0.00005), and the genotypic odds ratio for the (C;C) genotype was 1.6 (CI: 1.32-1.95, p<0.00005). Note that rs6275 and rs6277 are only 18bp apart, hence their very tight linkage (r²=1). C allele associated significantly (p = 0.021) with post-traumatic stress disorder in a sample of (assumedly Australian) 127 war veterans w/ 228 controls spittoon people with two As at rs6277(T;T) were better at NoGo learning. [pharmgkb] T allele associated with decrease ...

[PharmGKB:Curated Risk or phenotype-associated variant: C. Phenotype: The A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with atypical antipsychotic-induced obsessive compulsive symptoms. Study size: 94. Study population/ethnicity: Patients with schizophrenia receiving atypical antipsychotics; Asian; Korea. Significance metric(s): p = 0.04. Type of association: CO.]

In mice, the genetic locus best correlated to anxiety-related behaviour contains the 'regulator of G protein signaling 2' gene . In humans, SNPs in the equivalent RGS2 gene have now been studied to see if they are correlated to anxiety related disorders. In the first part of one study, 119 families including children underwent standard lab-based behavioural assessments of behavioural inhibition, defined as a heritable temperamental profile characterized by a tendency to be shy, avoident, and behaviourally restrained in situations that are novel or unfamiliar. Along with some other RGS2 SNPs, carriers of a rs4606(G) allele were 3 fold more likely to exhibit behavioural inhibition (CI: 1.31-6.84, p = 0.0026). In the second part of this study, 744 college undergraduates (228 men, 516 women) w...

rs518147, also known as -697G/C, is a SNP in the 5-hydroxytryptamine (serotonin) receptor 2C HTR2C gene. A study of 107 patients with schizophrenia being treated with olanzapine reported a protective effect against weight-gain from the (C) allele of this SNP; fewer patients (of 28) with a rs518147(C) allele had a body mass index increase of >=10% (p=0.0006), whereas (G;G) homozygotes did. This effect may also involve nearby SNP rs3813929. [PharmGKB:Curated This variant is associated with Olanzapine-induced weight gain. The -697C allele confers protective effect towards Olanzapine-induced weight gain in a study consisting of 107 patients with schizophrenia.]

rs4765623 is a SNP in the scavenger receptor class B, member 1 SCARB1 gene. In a study of 67 mostly Caucasian patients prescribed the atypical antipsychotic olanzapine, carriers of a rs4765623(C) allele were more likely to gain significant weight compared to rs4765623(T;T) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, rs5092 and rs7412, were also significantly associated with weight profiles in these patients. [GWAS:None]

rs6280, also known as '''Ser9Gly''', is a SNP in the dopamine receptor D3 DRD3 gene. The rs6280(C) allele encodes a glycine, and the (T) allele encodes a serine (in dbSNP orientation). In a study of 88 patients being treated for schizophrenia with olanzapine, those who were rs6280(C;C) homozygotes had greater positive symptom remission (endpoint rating of minimal or none on all PANSS clinical response positive items, 39.1%), as compared with (C;T) or (T;T) genotypes (13.8%; p = 0.033). Ser9Gly has been implicated in executive function in some studies, but the results are conflicting. * Gly/Gly carriers showed significantly (p = 0.002) poorer performance than Ser/Ser carriers on executive functioning tasks in a somewhat small Caucasian sample (84 patients with first-episode psychosis and 85...

rs1800497, a SNP also known as the TaqIA (or Taq1A) polymorphism of the dopamine D2 receptor DRD2 gene (even though it is actually located over 10,000bp downstream of the gene), gives rise to the DRD2*A1 allele. This allele (rs1800497(T)) is associated with a reduced number of dopamine binding sites in the brain , and has been postulated to play a role in alcoholism, smoking, and certain neuropsychiatric disorders. The reduced number of dopamine binding sites may play a role in nicotine addiction by causing an 'understimulated' state that can be relieved by smoking (and/or use of other drugs). A wide variety of reports have been published over more than ten years either linking rs1800497 to aspects of nicotine use and smoking cessation success, or finding no such association. A meta-analys...

rs4994, also known as Trp64Arg or as the Arg64 variant, is a SNP in the ADRB3 gene. The rs4994(C) allele encodes the variant arginine. In a study of 600+ women initially referred for coronary angiography and then followed for 6 years, during which time 115 experienced a heart problem, rs4994(C) individuals were calculated to be at higher risk (adjusted hazard ratio 2.10, CI: 1.05-4.24). This risk was due to subtle increases in risk for all of the individual endpoints, and was only seen in women without obstructive coronary artery disease. [PharmGKB:Curated Arg in position 64 associated with olanzapine-induced weight gain] [OMIM:OBESITY, SUSCEPTIBILITY TO]