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From SNPedia

Warfarin (Coumadin®)
Geno Mag Summary
(C;C) 1 normal; no risk of altered warfarin metabolism or NSAID metabolism
(C;T) 1.5 ~20% reduction in warfarin metabolism; some NSAID risk
(T;T) 2 ~ 40% reduction in warfarin metabolism, greater NSAID risk
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (classic)rs1799853
1000 genomesrs1799853
23andMe allrs1799853
GWAS Ctlgrs1799853
Max Magnitude2
? (C;C) (C;T) (T;T) 28
Risk Rs1799853(T;T)
Alt Rs1799853(T;T)
Reference Rs1799853(C;C)
Significance Other
Disease Warfarin response warfarin response - Dosage not specified
Variation info
Gene CYP2C9
CLNDBN Warfarin response warfarin response - Dosage not specified
Reversed 0
HGVS NC_000010.10:g.96702047C\x3d; NC_000010.10:g.96702047C>T
CLNSRC OMIM Allelic Variant PharmGKB Clinical Annotation UniProtKB (protein)
CLNACC RCV000150377.1, RCV000150378.1, RCV000008920.1, RCV000154312.1, RCV000211223.1, RCV000309101.1,

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This SNP has been recognized by the Coriell Personalized Medicine Collaborative ICOB.
Additional information is available here

rs1799853 is a SNP in the CYP2C9 gene and is linked to poor warfarin metabolism and risk of GI bleeding with some NSAID drugs.

The common nomenclature for this polymorphism is CYP2C9*2 (Cys amino acid, T allele; the SNP is also known as C430T or Cys144Arg).

[PMID 1305837] Advanced knowledge of this may influence initial warfarin dosing by physicians. Warfarin is monitored through INR (international normalized ratio) and proper dosing is influenced by a variety of factors including warfarin metabolism and diet.

[PMID 15608560] The rs1799853(T) allele encodes a variant amino acid, cysteine, which has been linked to poor metabolism of warfarin and thus sensitivity.

The CYP2C9*2 allele is also associated with higher sensitivity to the anti-epileptic drug phenytoin. Note however that the CPIC (and FDA) mention concurrent testing for the HLA-B*15:02 allele, since carriers are at significantly increased risk of Stevens-Johnson syndrome (SJS/PTEN).

[PMID 8004131] 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) [2].

[PMID 19422321] In a 2009 article titled "Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine?" Authors reviewed prior research that argued:

[PMID 18216720] In a 2008 article (reviewed in [PMID 19422321]) titled "Interaction of CYP2C8 and CYP2C9 genotypes modifies the risk for nonsteroidal anti-inflammatory drugs-related acute gastrointestinal bleeding," the study discovered that carriers of CYP2C8*3 (a minor allele of both rs10509681 and rs11572080) had a GI bleeding event risk OR=1.81 (95% CI=0.95–3.46; P=0.071) and risk increased if carriers drank more than 20g alcohol/day to an OR=1.99 (95% CI=1.06–3.74; P=0.034). As CYP2C8*3 and CYP2C9*2 rs1799853 variant alleles are in linkage disequilibrium, patients are likely to carry the risk allele to both 8*3 and 9*2, and when they do, The OR (95% CI) for carriers of such a genotype is increased to 1.94 (1.13–3.33), P=0.017.

[PMID 18216720OA-icon.png] A 2013 NIH review titled "PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 8" reiterated that "some data suggest that the combined presence of minor risk alleles CYP2C8*3 (rs10509681 and rs11572080) and CYP2C9*2 rs1799853 is a determinant of NSAID-induced gastrointestinal bleeding." They cited [PMID 18216720].

GWAS snp
PMID [PMID 19300499OA-icon.png]
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

[PMID 20214591] Pharmacogenomics in aspirin intolerance

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

[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

[PMID 17048007OA-icon.png] Association of warfarin dose with genes involved in its action and metabolism.

[PMID 17387222OA-icon.png] Genetic-based dosing in orthopedic patients beginning warfarin therapy.

[PMID 18305455OA-icon.png] Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin.

[PMID 18466099OA-icon.png] Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans.

[PMID 18547414OA-icon.png] Genotyping panel for assessing response to cancer chemotherapy.

[PMID 18574025OA-icon.png] The largest prospective warfarin-treated cohort supports genetic forecasting.

[PMID 18596683OA-icon.png] Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.

[PMID 18662264OA-icon.png] Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patients.

[PMID 18680736] Genetic factors contribute to patient-specific warfarin dose for Han Chinese.

[PMID 18752379OA-icon.png] Warfarin pharmacogenetics.

[PMID 18990750OA-icon.png] Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk.

[PMID 18992148OA-icon.png] Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study.

[PMID 18992263OA-icon.png] Colon tumor mutations and epigenetic changes associated with genetic polymorphism: insight into disease pathways.

[PMID 19223558OA-icon.png] Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma.

[PMID 19538716OA-icon.png] Thrombotic genetic risk factors and warfarin pharmacogenetic variants in Sao Miguel's healthy population (Azores).

[PMID 19761371OA-icon.png] Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.

[PMID 19955245OA-icon.png] Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.

[PMID 20082485OA-icon.png] Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women.

[PMID 20149073] Pharmacogenetics of acenocoumarol in patients with extreme dose requirements.

[PMID 20459744OA-icon.png] Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.

[PMID 20585445OA-icon.png] A novel, single algorithm approach to predict acenocoumarol dose based on CYP2C9 and VKORC1 allele variants.

[PMID 20733952OA-icon.png] Warfarin genotyping using three different platforms.

[PMID 20808793OA-icon.png] Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants?

[PMID 22010099] VKORC1 and CYP2C9 genotype and patient characteristics explain a large proportion of the variability in warfarin dose requirement among children.

[PMID 22486182] Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients.

[PMID 22569204OA-icon.png] PharmGKB summary: phenytoin pathway.

[PMID 23081681OA-icon.png] CYP2C9 variants increase risk of colorectal adenoma recurrence and modify associations with smoking but not aspirin treatment

[PMID 23473641] Effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients

[PMID 23587916] Allele frequency distribution of CYP2C9 2 and CYP2C9 3 polymorphisms in six Mexican populations

[PMID 24324947OA-icon.png] VKORC1 and CYP2C9 Genotype Variations in Relation to Warfarin Dosing in Korean Stroke Patients

[PMID 24368493] Interaction between ALOX5AP and CYP3A5 gene variants significantly increases the risk for cerebral infarctions in Chinese

[PMID 24380239] Characterization of the most common CYP2C9 and CYP2C19 allelic variants in the population from the Republic of Macedonia

[PMID 22676711OA-icon.png] Pharmacogenomics of warfarin in populations of African descent.

[PMID 23130019OA-icon.png] Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.

[PMID 23133420OA-icon.png] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.

[PMID 23691226OA-icon.png] Novel associations of VKORC1 variants with higher acenocoumarol requirements.

[PMID 26265036OA-icon.png] Genome-wide association study of warfarin maintenance dose in a Brazilian sample

[PMID 29425227OA-icon.png] Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations.

[PMID 30287909] Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence the response to anti-TNF therapy in rheumatoid arthritis patients.