From SNPedia
| Geno
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Mag
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Summary
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| (C;C)
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0.1
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normal; no change in warfarin metabolism
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| (C;T)
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CYP2C9*2 carrier; average 20% reduction in warfarin metabolism
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| (T;T)
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2.1
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CYP2C9*2 homozygote; average 40% reduction in warfarin metabolism
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| ? | (C;C) (C;T) (T;T) | 28 |
|---|
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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 [
PMID 15608560]. 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) [1] (NM_000771:c.430C>T, NP_000762:p.144R>C) [PMID 8004131] [2].
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 aceclofenac, celecoxib, diclofenac, ibuprofen, indomethazine, lornoxicam, meloxicam, naproxen, piroxicam, tenoxicam and valdecoxib.[PMID 19422321]
| GWAS snp
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| PMID
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[PMID 19300499]
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| Trait
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Warfarin maintenance dose
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| Title
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A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose
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| Risk Allele
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| P-val
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1E-31
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| Odds Ratio
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0.54 [0.45-0.63] mg/week decrease
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| PharmGKB | PA165111644 |
| Name | CYP2C9*2, c.430C>T, mRNA 455C>T, p.Arg144Cys |
| Annotation | Risk or phenotype-associated allele: rs1799853 T allele Phenotype: CYP2C9 wild-type (reference) allele carriers required a mean warfarin dose of 3.2 ± 1.6 mg, whereas patients carrying one or two CYP2C9 variant alleles (CYP2C9*2 = rs1799853 T allele, CYP2C9*3 = rs1057910 C allele, relative to CYP2C9*1 = reference) required significantly lower doses (*1/*x: 2.7 ± 1.5 mg (−16%); *x/*x: 1.9 ± 1.1 mg (−41%)) (p = 0.0015). CYP2C9 genotypes showed significant influence on the time to the first INR >=2 (p = 0.0016). The risk for having an INR value >=4 was higher in individuals with multiple variants of CYP2C9 or VKORC1 (rs9923231 A allele) (OR = 12.8, 95% CI = 2.73-60.0). The combined effect of variants and age, explained 26.6% of the variability in the warfarin dose, with VKORC1 (rs9923231 A allele) accounting for 19.1%, CYP2C9 (rs1799853 T allele, or rs1057910 C allele) for 3.2%, EPHX1 (rs2292566 A allele) for 1.7%, CYP4F2 (rs2108622 C allele) for 1.1%, and age for 1.5%. Study size: 283. Study population/ethnicity: Hospitalized Caucasian patients aged 75 years or older, recruited Sep 2002-Nov 2004 in Ivry, France, and Oct 2005-Mar 2008 from 14 French centers. Significance metric(s): p < = 0.0016. Type of association: GN; PK. |
| Gene | CYP2C9 |
| Featue | Exon/NonSyn |
| Evidence | PubMed ID:19794411 |
| Drugs | warfarin |
| Diseases | |
| Curation Level | Curated |
[PMID 20214591] Pharmacogenomics in aspirin intolerance
[PMID 20555338] Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements
| PharmGKB | PA164739916 |
| Name | |
| Annotation | GWAS results: A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose. (Initial Sample Size: 1,053 individuals; Replication Sample Size: 588 individuals); (Region: 10q23.33; Reported Gene(s): CYP2C9; Risk Allele: rs1799853-?); (p-value= 1E-31).This variant is associated with Warfarin maintenance dose. |
| Gene | CYP2C9 |
| Featue | Exon/NonSyn |
| Evidence | PubMed ID:19300499; Web Resource:http://www.genome.gov/gwastudies/ |
| Drugs | warfarin |
| Diseases | |
| Curation Level | Non-Curated |
| PharmGKB | PA162652683 |
| Name | CYP2C9*2, CYP2C9:144Arg>Cys |
| Annotation | This variant (CYP2C9*2) has been shown to influence warfarin dose and is included in the pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin. |
| Gene | CYP2C9 |
| Featue | Exon/NonSyn |
| Evidence | PubMed ID:19228618 |
| Drugs | warfarin |
| Diseases | |
| Curation Level | Curated |
| PharmGKB | PA165107375 |
| Name | CYP2C9*2, CYP2C9:Arg144Cys |
| Annotation | In a study of Scottish patients receiving sulfonylureas (n=1073), those with any CYP2C9*2 alleles were less likely to experience treatment failure, and CYP2C9*2 homozygotes had greater reductions in HbA(1c) than CYP2C9*1. |
| Gene | CYP2C9 |
| Featue | Exon/NonSyn |
| Evidence | PubMed ID:19794412 |
| Drugs | glibenclamide, gliclazide, glimepiride, glipizide |
| Diseases | Diabetes Mellitus |
| Curation Level | Curated |
| PharmGKB | PA165111640 |
| Name | CYP2C9*2, c.430C>T, mRNA 455C>T, p.Arg144Cys |
| Annotation | Risk or phenotype-associated allele: CYP2C9*2, rs1799853 T allele, Cys144. Phenotype: Drug response phenotypes included (1) reaching target HbA(1c), (2) maximum HbA(1c) reduction, and (3) time to monotherapy failure. Patients homozygous for the loss-of-function CYP2C9 alleles (*2/*2, *2/*3, *3/*3) achieved greater treatment target (OR = 3.4, p = 0.0009), 0.5% greater reduction in target HbA1c concentration (p = 0.003), and lower risk of monotherapy failure based an additive genetic model (allelic hazard ratio 0.79, 95% confidence interval 0.63-0.99, p = 0.04), compared to wild-type allele (*1) carriers. Study size: 1,073 patients (578 drug-naive, 495 with prior and continued metformin exposure). Study population/ethnicity: Diabetes patients recruited in Tayside, Scotland for the Diabetes Audit and Research Tayside Study (DARTS), between 1992 and 2007, who were incident sulfonylurea users. Significance metric(s): p = (0.04 - 0.0009) Type of association: GN; PD |
| Gene | CYP2C9 |
| Featue | Exon/NonSyn |
| Evidence | PubMed ID:19794412 |
| Drugs | glibenclamide, gliclazide, glimepiride, glipizide, metformin |
| Diseases | Diabetes Mellitus, Type 2 |
| Curation Level | Curated |
| OMIM | 601130 |
| Desc | CYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 9; CYP2C9 |
| Variant | |
| Related | also |
[PMID 22118051] Genetic variants in CYP (-1A2, -2C9, -2C19, -3A4 and -3A5), VKORC1 and ABCB1 genes in a black South African population: a window into diversity
