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rs9923231

From SNPedia

Warfarin (Coumadin®)
Orientationplus
Stabilizedplus
Geno Mag Summary
(C;C) 0 normal
(C;T) 2 reduced warfarin dose if treated for VTE
(T;T) 2.1 reduced warfarin dose if treated for VTE
ReferenceGRCh38 38.1/141
Chromosome16
Position31096368
GeneVKORC1
is asnp
is mentioned by
dbSNPrs9923231
ebirs9923231
HLIrs9923231
Exacrs9923231
Varsomers9923231
Maprs9923231
PheGenIrs9923231
hapmaprs9923231
1000 genomesrs9923231
hgdprs9923231
ensemblrs9923231
gopubmedrs9923231
geneviewrs9923231
scholarrs9923231
googlers9923231
pharmgkbrs9923231
gwascentralrs9923231
openSNPrs9923231
23andMers9923231
23andMe allrs9923231
SNP Nexus

SNPshotrs9923231
SNPdbers9923231
MSV3drs9923231
GWAS Ctlgrs9923231
Merged fromRs17878363
GMAF0.4679
Max Magnitude2.1
? (C;C) (C;T) (T;T) 28
CPMC Logo.png

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

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.
  • VKORC1*2.

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 18523153OA-icon.png]

OMIM122700
DescCOUMARIN RESISTANCE
Variant
Relatedalso
OMIM608547
DescVITAMIN K EPOXIDE REDUCTASE COMPLEX, SUBUNIT 1; VKORC1
Variant
Relatedalso
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 T
P-val 0
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

GWAS snp
PMID [PMID 20833655]
Trait
Title Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese
Risk Allele
P-val 9E-31
Odds Ratio None None






OMIM608547
Desc
Variant0006
Relatedalso
[PMID 21179439OA-icon.png] 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 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 17635701] VKORC1: molecular target of coumarins.


[PMID 18252229OA-icon.png] Warfarin pharmacogenetics: CYP2C9 and VKORC1 genotypes predict different sensitivity and resistance frequencies in the Ashkenazi and Sephardi Jewish populations.


[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 18559094OA-icon.png] Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction.


[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 18809808OA-icon.png] Ethnic differences in cardiovascular drug response: potential contribution of pharmacogenetics.


[PMID 18855533OA-icon.png] VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans.


[PMID 19074728OA-icon.png] Relative contribution of CYP2C9 and VKORC1 genotypes and early INR response to the prediction of warfarin sensitivity during initiation of therapy.


[PMID 19538716OA-icon.png] 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 19955245OA-icon.png] 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 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 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.


GET Evidence
rs9923231
aa_change
aa_change_short
impact pathogenic
qualified_impact Insufficiently evaluated pathogenic
overall_frequency 0.34375
summary



[PMID 23124848OA-icon.png] 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 23662025OA-icon.png] 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 22676711OA-icon.png] Pharmacogenomics of warfarin in populations of African descent.


[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.


ClinVar
Risk rs9923231(A,G,T;A,G,T)
Alt rs9923231(A,G,T;A,G,T)
Reference rs9923231(C;C)
Significance Drug-response
Disease Warfarin response warfarin response - Efficacy warfarin response - Dosage warfarin response - Toxicity/ADR acenocoumarol response - Dosage phenprocoumon response - Dosage
Variation info
Gene VKORC1
CLNDBN Warfarin response warfarin response - Efficacy warfarin response - Dosage warfarin response - Toxicity/ADR acenocoumarol response - Dosage phenprocoumon response - Dosage
Reversed 0
HGVS NC_000016.9:g.31107689C\x3d; NC_000016.9:g.31107689C>A; NC_000016.9:g.31107689C>T
CLNSRC PharmGKB Clinical Annotation PharmGKB OMIM Allelic Variant
CLNACC RCV000152659.1, RCV000211206.1, RCV000211210.1, RCV000211327.1, RCV000211333.1, RCV000211421.1, RCV000002295.2,



[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