|(C;T)||2||reduced warfarin dose if treated for VTE|
|(T;T)||2.1||reduced warfarin dose if treated for VTE|
Several SNPs in the VKORC1 gene have been linked to warfarin sensitivity, with perhaps the most common being this SNP rs9923231. Note that the orientation as published in scientific articles is often on the opposite strand compared to the orientation in dbSNP, so you will sometimes see it as a G>T snp. It is also known as
- -1639G>A with the minus indicating that this is in an upstream promoter
- 3673 based on its position in GenBank accession number AY587020.
The main findings related to the treatment of venous thromboembolism (aka VTE; from hypercoagulability) with the blood thinner warfarin for this SNP are that carriers of the rs9923231(T) allele require significantly reduced doses of warfarin, and are (otherwise) at a higher risk of serious bleeding. [PMID 15930419]
Clinical studies demonstrate that rs9923231(A), and the tightly linked intron1 SNP rs9934438(T) predict warfarin dose more accurately than intron 2 SNP 1542G>C in blacks. Increased warfarin dose requirement in blacks was accounted for by lower frequency of the rs9923231(T) allele. Therefore, the T allele at rs9923231 is a suitable biomarker for warfarin dosing across ethnic populations. [PMID 18523153]
|Trait||Warfarin maintenance dose|
|Title||A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose|
|Odds Ratio||0.97 [0.91-1.02] mg/week decrease|
[PMID 20555338] Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements
[PMID 20842355] VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China
|Title||Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese|
|Odds Ratio||None None|
[PMID 21179439] VKORC1 common variation and bone mineral density in the Third National Health and Nutrition Examination Survey
[PMID 22321278] [Impact of CYP2C9 and VKORC1 polymorphism on warfarin response during initiation of therapy]
[PMID 16270629] VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation.
[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 17635701] VKORC1: molecular target of coumarins.
[PMID 18252229] Warfarin pharmacogenetics: CYP2C9 and VKORC1 genotypes predict different sensitivity and resistance frequencies in the Ashkenazi and Sephardi Jewish populations.
[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 18559094] Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction.
[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 18809808] Ethnic differences in cardiovascular drug response: potential contribution of pharmacogenetics.
[PMID 18855533] VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans.
[PMID 19074728] Relative contribution of CYP2C9 and VKORC1 genotypes and early INR response to the prediction of warfarin sensitivity during initiation of therapy.
[PMID 19538716] Thrombotic genetic risk factors and warfarin pharmacogenetic variants in Sao Miguel's healthy population (Azores).
[PMID 19875892] A vitamin K epoxide reductase-oxidase complex gene polymorphism (-1639G>A) and interindividual variability in the dose-effect of vitamin K antagonists.
[PMID 19955245] Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.
[PMID 20017677] ARMS test for diagnosis of CYP2C9 and VKORC1 mutation in patients with pulmonary embolism in Han Chinese.
[PMID 20149073] Pharmacogenetics of acenocoumarol in patients with extreme dose requirements.
[PMID 20193673] Genotype polymorphisms of GGCX, NQO1, and VKORC1 genes associated with risk susceptibility in patients with large-artery atherosclerotic stroke.
[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 22010099] VKORC1 and CYP2C9 genotype and patient characteristics explain a large proportion of the variability in warfarin dose requirement among children.
[PMID 22178823] [Distribution of variant alleles association with warfarin pharmacokinetics and pharmacodynamics in the Han population in China].
[PMID 22486182] Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients.
|qualified_impact||Insufficiently evaluated pathogenic|
[PMID 23124848] SNPs in VKORC1 are risk factors for systemic lupus erythematosus in asians
[PMID 23473641] Effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients
[PMID 23104259] Influence of warfarin dose-associated genotypes on the risk of hemorrhagic complications in Chinese patients on warfarin
[PMID 23662025] Genetic variation and haplotype structure of the gene Vitamin K epoxide reductase complex, subunit 1 in the Tamilian population
[PMID 23732872] Association of VKORC1-1639G>A polymorphism with susceptibility to ossification of the posterior longitudinal ligament of the spine: a Korean study
[PMID 23835662] Pharmacogenomics, ancestry and clinical decision making for global populations
[PMID 22592842] Oral anticoagulation and VKORC1 polymorphism in patients with a mechanical heart prosthesis: a 6-year follow-up.
[PMID 22676711] Pharmacogenomics of warfarin in populations of African descent.
[PMID 23133420] Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.
[PMID 23691226] Novel associations of VKORC1 variants with higher acenocoumarol requirements.
|Risk||rs9923231(A;A) rs9923231(G;G) Rs9923231(T;T)|
|Alt||rs9923231(A;A) rs9923231(G;G) Rs9923231(T;T)|
|Disease||Warfarin response warfarin response - Efficacy warfarin response - Dosage warfarin response - Toxicity/ADR acenocoumarol response - Dosage phenprocoumon response - Dosage not provided|
|CLNDBN||Warfarin response warfarin response - Efficacy warfarin response - Dosage warfarin response - Toxicity/ADR acenocoumarol response - Dosage phenprocoumon response - Dosage not provided|
|HGVS||NC_000016.9:g.31107689C\x3d; NC_000016.9:g.31107689C>A; NC_000016.9:g.31107689C>T|
|CLNSRC||PharmGKB Clinical Annotation OMIM Allelic Variant|
|CLNACC||RCV000152659.1, RCV000211206.1, RCV000211210.1, RCV000211327.1, RCV000211333.1, RCV000211421.1, RCV000002295.2, RCV000377657.1,|
[PMID 25069408] Multiplex pyrosequencing method to determine CYP2C9*3, VKORC1*2, and CYP4F2*3 polymorphisms simultaneously: its application to a Korean population and comparisons with other ethnic groups