Rs1799853
| Warfarin (Coumadin®) |
| Orientation | plus |
| is a | snp |
| is | mentioned by |
| dbSNP | rs1799853 |
| PheGenI | rs1799853 |
| nextbio | rs1799853 |
| hapmap | rs1799853 |
| 1000 genomes | rs1799853 |
| hgdp | rs1799853 |
| ensembl | rs1799853 |
| gopubmed | rs1799853 |
| geneview | rs1799853 |
| scholar | rs1799853 |
| rs1799853 | |
| pharmgkb | rs1799853 |
| gwascentral | rs1799853 |
| openSNP | rs1799853 |
| 23andMe | rs1799853 |
| 23andMe all | rs1799853 |
| SNP Nexus | |
| SNPshot | rs1799853 |
| SNPdbe | rs1799853 |
| MSV3d | rs1799853 |
| Gene | CYP2C9 |
| Chromosome | 10 |
| Orientation | plus |
| Position | 96702047 |
| Reference | GRCh37 37.1/131 |
| Max Magnitude | 2.1 |
| 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 |
|---|---|---|
| This SNP has been recognized by the Coriell Personalized Medicine Collaborative ICOB.
|
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 |
[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
| ClinVar | |
|---|---|
| Risk | rs1799853(T;T) |
| Normal | rs1799853(C;C) |
| Significance | 6 |
| Disease | Warfarin response |
| ClinVar | info |
| Gene | CYP2C9 |
| CLNDBN | Warfarin response |
| Reversed | 0 |
| CLNHGVS | NC_000010.10:g.96702047C>T |
| CLNSRC | OMIM Allelic Variant |
[PMID 17048007] Association of warfarin dose with genes involved in its action and metabolism.
[PMID 17387222] Genetic-based dosing in orthopedic patients beginning warfarin therapy.
[PMID 18305455] Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin.
[PMID 18466099] Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans.
[PMID 18547414] Genotyping panel for assessing response to cancer chemotherapy.
[PMID 18574025] The largest prospective warfarin-treated cohort supports genetic forecasting.
[PMID 18596683] Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.
[PMID 18662264] 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 18752379] Warfarin pharmacogenetics.
[PMID 18990750] Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk.
[PMID 18992148] Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study.
[PMID 18992263] Colon tumor mutations and epigenetic changes associated with genetic polymorphism: insight into disease pathways.
[PMID 19223558] Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma.
[PMID 19538716] Thrombotic genetic risk factors and warfarin pharmacogenetic variants in Sao Miguel's healthy population (Azores).
[PMID 19761371] Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.
[PMID 19955245] Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.
[PMID 20082485] 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 20459744] Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.
[PMID 20585445] A novel, single algorithm approach to predict acenocoumarol dose based on CYP2C9 and VKORC1 allele variants.
[PMID 20733952] Warfarin genotyping using three different platforms.
[PMID 20808793] 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 22569204] PharmGKB summary: phenytoin pathway.
[PMID 23081681] CYP2C9 variants increase risk of colorectal adenoma recurrence and modify associations with smoking but not aspirin treatment
| 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. |
[PMID 23473641] Effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients
