Promethease Report

23andMe reports that the T allele of rs3918290 is associated with the rare recessive disorder dihydropyrimidine dehydrogenase deficiency (DPD), also known as hereditary thymine-uraciluria or familial pyrimidinemia. pharmgkb - defines *2A allele, which has a significantly higher chance of 5-fluorouracil toxicity 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) Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4) cause autosomal recessive anonychia. Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine. Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate. Variants in the ITPA gene protect a...

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. 23an...

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.]

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...

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...

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: 23andMe blog 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 estima...

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: 23andMe blog '''Note:''' the orientation of this SNP in SNPedia is as detailed in dbSNP, but in publications (including 23andMe's blog) the orientation is 'flipped', so what's (A;A) in dbSNP is (T;T) as discussed by the 23andMe blog.

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]

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.' A brain...

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...

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]

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 its 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, both...

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). ...

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...

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...

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;...

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. 23an...

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.]

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...

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...

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...

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...

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]

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]

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. 23an...

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]

Pharmacogenetics of antidepressant response. [GWAS:Treatment response to citalopram]

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.]

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...

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).

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. Clopidogrel Efficacy [Pharm...

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. Clopidogrel Efficacy [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.]

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). Clopidogrel Efficacy [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.

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...

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

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. Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms. [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 gr...

The rs1799971(G) allele in exon 1 of the mu opioid 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 (...

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 ...

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...

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 (-) 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. Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms. [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 gr...

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 ...

rs671 is a classic SNP, well known in a sense through the phenomena known as the 'alcohol flush', also known as the 'Asian Flush' or 'Asian blush', in which certain individuals, often of Asian descent, have their face, neck and sometimes shoulders turn red after drinking alcohol. The rs671(A) allele of the ALDH2 gene is the culprit, in that it encodes a form of the aldehyde dehydrogenase 2 protein that is defective at metabolizing alcohol. This allele is known as the ALDH*2 form, and individuals possessing either one or two copies of it show alcohol-related sensitivity responses including facial flushing, and severe hangovers (and hence they are usually not regular drinkers). Perhaps not surprisingly they appear to suffer less from alcoholism and alcohol-related liver disease. Disulfiram (...

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...

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. Clopidogrel Efficacy [Pharm...

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). Clopidogrel Efficacy [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]

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: 23andMe blog 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 estima...

rs2231142, also known as Q141K and C421A, is a SNP in the ABCG2 gene, indicating a missense variant. 'Our data indicate that at least 10% of all gout cases in whites are attributable to this causal 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 high...

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...

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.]

Carriers of the C allele at rs6139030 have a higher risk of developing thrombocytopenia when treated with interferon. Hepatitis C Treatment Side Effects [GWAS:None]

rs2231142, also known as Q141K and C421A, is a SNP in the ABCG2 gene, indicating a missense variant. 'Our data indicate that at least 10% of all gout cases in whites are attributable to this causal 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 high...

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...

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...

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. Clopidogrel Efficacy [Pharm...

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). Clopidogrel Efficacy [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]

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...

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. Clopidogrel Efficacy [Pharm...

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). Clopidogrel Efficacy [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 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 rs1799971(G) allele in exon 1 of the mu opioid 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 (...

The rs1799971(G) allele in exon 1 of the mu opioid 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 (...

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...

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.]

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...

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. Clopidogrel Efficacy [Pharm...

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). Clopidogrel Efficacy [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]

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...

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. Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms. [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 gr...

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 ...

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 Apoε2 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. Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and o...

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...

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. Clopidogrel Efficacy [Pharm...

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). Clopidogrel Efficacy [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]

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...

rs17238540, also known as SNP 29, is located in the HMG-CoA reductase HMGCR gene. The protein encoded by this gene is the target for drugs designed to inhibit its action, in order to lower cholesterol levels. SNPs in the HMGCR gene may affect how well such drugs (typically statins) work. In a study of ~1,500 patients treated with 40mg/d of pravastatin, rs17238540(G;T) heterozgyotes had a mean decrease in total cholesterol of 32.5 mg/dL (0.85 mmol/L), while the mean change for rs17238540(T;T) homozygotes was 41.8 mg/dL (1.09 mmol/L), a reduction in overall efficacy of 22.3% (absolute difference, 9.3 mg/dL, CI: 3.8-14.7 mg/dL, p<.001). The drop in total cholesterol was almost completely due to the decrease in LDL cholesterol, as there was no significant difference in the change in HDL cho...

rs17244841, also known as SNP 12, is located in the HMG-CoA reductase HMGCR gene. The protein encoded by this gene is the target for drugs designed to inhibit its action, in order to lower cholesterol levels. SNPs in the HMGCR gene may affect how well such drugs (typically statins) work. In a study of ~1,500 patients treated with 40mg/d of pravastatin, rs17244841(A;T) heterozgyotes had a mean decrease in total cholesterol of –32.8 mg/dL (–0.85 mmol/L), while the mean change for rs17244841(A;A) homozygotes was –42.0 mg/dL (–1.09 mmol/L), a reduction in overall efficacy of 21.8% (absolute difference, 9.2 mg/dL, CI: 3.8-14.6 mg/dL, p=.001). The drop in total cholesterol was almost completely due to the decrease in LDL cholesterol, as there was no significant difference in the change i...

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...

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. Clopidogrel Efficacy [Pharm...

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). Clopidogrel Efficacy [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]

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...

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. Clopidogrel Efficacy [Pharm...

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). Clopidogrel Efficacy [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]

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). Clopidogrel Efficacy [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]

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...

among 120 (likely Japanese) first-episode neuroleptic-naive schizophrenics treated with risperidone genotyped for 30 variants in misc. dopamine and serotonin (receptors and otherwise) two SNPs in DRD2 (rs1799989 and rs1800497) and two SNPs in AKT1 (rs3803300 and rs2494732) were significant predictors of treatment response to risperidone

rs1801028 is a SNP in the dopamine D2 receptor DRD2 gene. A meta-analysis comprising 27 samples and over 3,707 schizophrenia patients concluded that Cys/Ser heterozygotes, i.e. rs1801028(C;G) genotypes, were at elevated risk for schizophrenia when compared to either homozygote genotype (rs1801028(C;C) or rs1801028(G;G)). The odds ratio was 1.4 (p<0.005). An earlier meta-analysis comprising over 9,000 schizophrenia patients concluded pretty much the same thing: the Cys311 (rs1801028(G)) allele frequency led to an odds ratio of 1.43 (CI: 1.16-1.78, p<0.001) for this risk allele. A study of ~120 Chinese patients with schizophrenia concluded that Cys/Ser heterozygotes may not respond to risperidone treatment as well as Ser/Ser homozygotes. A paper has been published describing mistakes m...

rs2231142, also known as Q141K and C421A, is a SNP in the ABCG2 gene, indicating a missense variant. 'Our data indicate that at least 10% of all gout cases in whites are attributable to this causal 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 high...

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...

[GWAS:Response to statin therapy]

[GWAS:Response to statin therapy]

[GWAS:Response to statin therapy]

rs17238540, also known as SNP 29, is located in the HMG-CoA reductase HMGCR gene. The protein encoded by this gene is the target for drugs designed to inhibit its action, in order to lower cholesterol levels. SNPs in the HMGCR gene may affect how well such drugs (typically statins) work. In a study of ~1,500 patients treated with 40mg/d of pravastatin, rs17238540(G;T) heterozgyotes had a mean decrease in total cholesterol of 32.5 mg/dL (0.85 mmol/L), while the mean change for rs17238540(T;T) homozygotes was 41.8 mg/dL (1.09 mmol/L), a reduction in overall efficacy of 22.3% (absolute difference, 9.3 mg/dL, CI: 3.8-14.7 mg/dL, p<.001). The drop in total cholesterol was almost completely due to the decrease in LDL cholesterol, as there was no significant difference in the change in HDL cho...

rs17244841, also known as SNP 12, is located in the HMG-CoA reductase HMGCR gene. The protein encoded by this gene is the target for drugs designed to inhibit its action, in order to lower cholesterol levels. SNPs in the HMGCR gene may affect how well such drugs (typically statins) work. In a study of ~1,500 patients treated with 40mg/d of pravastatin, rs17244841(A;T) heterozgyotes had a mean decrease in total cholesterol of –32.8 mg/dL (–0.85 mmol/L), while the mean change for rs17244841(A;A) homozygotes was –42.0 mg/dL (–1.09 mmol/L), a reduction in overall efficacy of 21.8% (absolute difference, 9.2 mg/dL, CI: 3.8-14.6 mg/dL, p=.001). The drop in total cholesterol was almost completely due to the decrease in LDL cholesterol, as there was no significant difference in the change i...

rs776746, also known as 6986G>A, is a SNP encoding the (nonfunctional) CYP3A5*3 allele of the CYP3A5 gene. CYP3A5*3 has been studied especially in connection with the metabolism of tacrolimus, an immunosuppressive drug used in organ transplantation. The optimal therapeutic dose is in a relatively narrow window, so blood concentration monitoring is recommended. CYP3A5*3 carriers tend to build up higher levels of tacrolimus than CYP3A5*1 carriers, unless their tacrolimus intake is reduced. Risk of testicular germ cell cancer in relation to variation in maternal and offspring cytochrome p450 genes involved in catechol estrogen metabolism. Polymorphisms in the cytochrome P450 genes CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1, CYP19A1 and colorectal cancer risk. Prevalence of common dis...

rs6025 represents a SNP in the Factor V F5 gene, encoding a change in the protein from an arginine at position 506 to a glutamine. The resulting rs6025(A) allele encodes a mutation known as the Leiden mutation, R506Q, found in perhaps 3 to 5% of the individuals in most populations. About 1 in 10 individuals harboring the R506Q will experience clinically significant venous thromboembolism in their lifetimes (according to OMIM). Overall, the rs6025(A) allele appears to be necessary but not sufficient for the development of venous thromboembolism. Patients who are rs6025(A;G) heterozygotes but lack other risk-enhancing SNPs have a risk of recurrent deep venous thrombosis equal to patients with no such SNPs. In contrast, patients who are heterozygotes for both rs6025 and the prothrombin rs1799...

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...

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: 23andMe blog '''Note:''' the orientation of this SNP in SNPedia is as detailed in dbSNP, but in publications (including 23andMe's blog) the orientation is 'flipped', so what's (A;A) in dbSNP is (T;T) as discussed by the 23andMe blog.

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. Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms. [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 gr...

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...

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...

A genome-wide association study of acenocoumarol maintenance dosage. [PharmGKB:Curated In a GWAS study, this SNP was modestly associated with warfarin dose, accounting for ~9% of the variance in dose. This SNP was in perfect linkage disequilibrium with rs4917639.] [GWAS:Warfarin maintenance dose]

Warfarin [GWAS:None]

PharmGKB indicates that this SNP is relevant to Warfarin dosing. rs339097(G) is associated with 14.5% higher therapeutic warfarin dose in African Americans. This variant is also more common in African Americans with minor allele frequencies of 11–14% , but only 0.2% in Caucasians. Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients. [PharmGKB:Curated Risk or phenotype-associated allele: G allele was associated with higher required warfarin dose. Phenotype: The G allele of this SNP was associated with a 14.5% (SD +/- 7%) higher therapeutic warfarin dose in African Americans. Study size/population/ethnicity: Discovery cohort was 108 outliers(53 patients in the low dose group and 55 in the high dose group) selected from patients who attended an outp...

rs1057911 is a SNP in the CYP2C9 gene. The rs1057911(T) allele defines the CYP2C9_50298A>T variant, about which little is known. Warfarin

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: 23andMe blog 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 estima...