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rs1799853

From SNPedia

Warfarin (Coumadin®)
Orientationplus
Stabilizedplus
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
Chromosome10
Position94942290
GeneCYP2C9
is asnp
is mentioned by
dbSNPrs1799853
dbSNP (old)rs1799853
ClinGenrs1799853
ebirs1799853
HLIrs1799853
Exacrs1799853
Varsomers1799853
Maprs1799853
PheGenIrs1799853
Biobankrs1799853
1000 genomesrs1799853
hgdprs1799853
ensemblrs1799853
gopubmedrs1799853
geneviewrs1799853
scholarrs1799853
googlers1799853
pharmgkbrs1799853
gwascentralrs1799853
openSNPrs1799853
23andMers1799853
23andMe allrs1799853
SNP Nexus

SNPshotrs1799853
SNPdbers1799853
MSV3drs1799853
GWAS Ctlgrs1799853
GMAF0.06841
Max Magnitude2
? (C;C) (C;T) (T;T) 28
GET Evidence
CYP2C9-R144C
aa_change Arg144Cys
aa_change_short R144C
impact pharmacogenetic
qualified_impact Moderate clinical importance, pharmacogenetic
overall_frequency 0.0970982
summary This variant, also called CYP2C9*2, is a pharmacogenetic variant that modulates sensitivity for Warfarin (due to reduced metabolism). This variant is associated with Caucasians. The FDA has approved reduced recommended Warfarin dosage based on the presence of this variant.


ClinVar
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,


OMIM601130
DescCYTOCHROME P450, SUBFAMILY IIC, POLYPEPTIDE 9; CYP2C9
Variant
Relatedalso
OMIM601130
Desc
Variant0002
Relatedalso
CPMC Logo.png

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