Rs1799853

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dbSNPrs1799853
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SNP Nexus

SNPshotrs1799853
SNPdbers1799853
MSV3drs1799853
GeneCYP2C9
Chromosome10
Orientationplus
Position96702047
ReferenceGRCh37 37.1/131
Max Magnitude2.1
Geno Mag Summary
(C;C) 0.1 normal; no change in warfarin metabolism
(C;T) CYP2C9*2 carrier; average 20% reduction in warfarin metabolism
(T;T) 2.1 CYP2C9*2 homozygote; average 40% reduction in warfarin metabolism
? (C;C) (C;T) (T;T) 28
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 [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
PMID [PMID 19300499]
Trait Warfarin maintenance dose
Title A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose
Risk Allele
P-val 1E-31
Odds Ratio 0.54 [0.45-0.63] mg/week decrease
PharmGKBPA165111644
NameCYP2C9*2, c.430C>T, mRNA 455C>T, p.Arg144Cys
AnnotationRisk 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.
GeneCYP2C9
FeatueExon/NonSyn
EvidencePubMed ID:19794411
Drugswarfarin
Diseases
Curation LevelCurated


[PMID 20214591] Pharmacogenomics in aspirin intolerance

[PMID 20555338] Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements

PharmGKBPA161145194
NameCYP2C9*2, CYP2C9:144Arg>Cys
AnnotationThis variant has been shown to influence warfarin dose as well as affecting the clearance of several other drugs.
GeneCYP2C9
FeatueExon/NonSyn
EvidenceWeb Resource:http://www.pharmgkb.org/search/annotatedGene/cyp2c9/variant.jsp#ImportantVariantInformationforCYP2C9-111
Drugsfluvastatin, glipizide, phenytoin, tolbutamide, warfarin
Diseases
Curation LevelIn-Depth
PharmGKBPA164739916
Name
AnnotationGWAS 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.
GeneCYP2C9
FeatueExon/NonSyn
EvidencePubMed ID:19300499; Web Resource:http://www.genome.gov/gwastudies/
Drugswarfarin
Diseases
Curation LevelNon-Curated
PharmGKBPA162652683
NameCYP2C9*2, CYP2C9:144Arg>Cys
AnnotationThis 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.
GeneCYP2C9
FeatueExon/NonSyn
EvidencePubMed ID:19228618
Drugswarfarin
Diseases
Curation LevelCurated
PharmGKBPA165107375
NameCYP2C9*2, CYP2C9:Arg144Cys
AnnotationIn 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.
GeneCYP2C9
FeatueExon/NonSyn
EvidencePubMed ID:19794412
Drugsglibenclamide, gliclazide, glimepiride, glipizide
DiseasesDiabetes Mellitus
Curation LevelCurated
PharmGKBPA165111640
NameCYP2C9*2, c.430C>T, mRNA 455C>T, p.Arg144Cys
AnnotationRisk 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
GeneCYP2C9
FeatueExon/NonSyn
EvidencePubMed ID:19794412
Drugsglibenclamide, gliclazide, glimepiride, glipizide, metformin
DiseasesDiabetes Mellitus, Type 2
Curation LevelCurated
OMIM601130
DescCYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 9; CYP2C9
Variant
Relatedalso
OMIM601130
Desc
Variant0002
Relatedalso


[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

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