{{Rsnum
|rsid=9923231
|Gene=VKORC1
|Chromosome=16
|position=31096368
|Orientation=plus
|GMAF=0.4679
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|Summary=Warfarin (Coumadin®)
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=VKORC1
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 39.8 | 40.7 | 19.5
| HCB | 0.0 | 9.5 | 90.5
| JPT | 0.0 | 18.6 | 81.4
| YRI | 93.9 | 6.1 | 0.0
| ASW | 84.2 | 10.5 | 5.3
| CHB | 0.0 | 9.5 | 90.5
| CHD | 0.9 | 16.5 | 82.6
| GIH | 65.3 | 32.7 | 2.0
| LWK | 88.2 | 11.8 | 0.0
| MEX | 29.3 | 48.3 | 22.4
| MKK | 69.9 | 28.2 | 1.9
| TSI | 27.5 | 51.0 | 21.6
| HapMapRevision=28
}}{{CPMC SNP
|link=https://cpmc.coriell.org/Sections/Results/Warfarin.aspx?PgId=222
}}
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|18523153|OA=1
}}

{{omim
|desc=COUMARIN RESISTANCE
|id=122700
|rsnum=9923231
}}

{{omim
|id=608547
|desc=VITAMIN K EPOXIDE REDUCTASE COMPLEX, SUBUNIT 1; VKORC1
|rsnum=9923231
}}
{{PMID Auto GWAS
|PMID=19300499
|Trait=Warfarin maintenance dose
|Title=A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose
|RiskAllele=T
|Pval=0
|OR=0.97
|ORtxt=[0.91-1.02] mg/week decrease
|OA=1
}}

{{PharmGKB
|RSID=rs9923231
|Name_s=upstream -1639G>A
|Gene_s=VKORC1
|Feature=NA
|Evidence=PubMed ID:19794411
|Annotation=Risk or phenotype-associated allele: A allele Phenotype: This A allele was associated with a lower warfarin maintenance dose according to a gene-dose effect (1.9 &#177; 1.2 mg (&#8722;50%) for AA homozygotes, 2.8 &#177; 1.3 mg (&#8722;26%) for GA heterozygotes, 3.8 &#177; 1.6 mg in GG homozygotes) (p < 0.0001). The A allele was associated with shorter median time to the first INR >=2 (3 vs. 6 vs. 8 days for AA, GA, and GG genotypes, respectively) (p = 0.0003). Risk for having an INR value >=4 was higher in individuals the A allele or CYP2C9 variants (rs1799853 T allele, rs1057910 C allele) (OR = 12.8; 95% CI = 2.73-60.0). The combined effect of variants and age explained 26.6% of the warfarin dose variability, with VKORC1 (rs9923231 A allele) accounting for 19.1%, CYP2C9 (rs1799853 T allele, or rs1057910 C allele) for 3.2%, EPHX1 (rs2292566 A allele) for 1.7%, CYP4F2 (rs2108622 C allele) for 1.1%, and age for 1.5%. Study size: 283. Study population/ethnicity: Hospitalized Caucasian patients aged 75 years or older, recruited Sep 2002-Nov 2004 in Ivry, France, and Oct 2005-Mar 2008 from 14 French centers. Significance metric(s): p < = 0.003. Type of association: GN; PK.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165111643
}}

{{PMID Auto
|PMID=20555338
|Title=Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements
}}
{{PMID Auto
|PMID=20842355
|Title=VKORC1-1639G&gt;A, CYP2C9, EPHX1691A&gt;G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China
}}
{{PMID Auto GWAS
|PMID=20833655
|Trait=None
|Title=Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese
|RiskAllele=
|Pval=9E-31
|OR=None
|ORtxt=None
}}

{{PharmGKB
|RSID=rs9923231
|Name_s=VKORC1:G3673A; VKORC1:-1639G>A
|Gene_s=VKORC1
|Feature=NA
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/vkorc1/variant.jsp#ImportantVariantInformationforVKORC1-3673
|Annotation=Believed to be the causative allele for the low dose phenotype in warfarin therapy based on both in vitro and in vivo evidence
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145140
}}

{{PharmGKB
|RSID=rs9923231
|Name_s=VKORC1:-1639
|Gene_s=VKORC1
|Feature=NA
|Evidence=PubMed ID:18535201
|Annotation=In a GWAS study, this SNP was strongly associated with stabilized warfarin dose, and was in perfect linkage disequilibrium with rs10871454.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA161748415
}}

{{PharmGKB
|RSID=rs9923231
|Name_s=
|Gene_s=VKORC1
|Feature=NA
|Evidence=PubMed ID:19300499; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose. (Initial Sample Size: 1,053 individuals; Replication Sample Size: 588 individuals); (Region: 16p11.2; Reported Gene(s): VKORC1; Risk Allele: rs9923231-T); (p-value= 0).This variant is associated with Warfarin maintenance dose.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164739914
}}

{{PharmGKB
|RSID=rs9923231
|Name_s=VKORC1:G3673A; VKORC1:-1639G>A
|Gene_s=VKORC1
|Feature=NA
|Evidence=PubMed ID:19228618
|Annotation=This promoter SNP is believed to be the causative SNP for the warfarin low dose phenotype. It is included in the pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin.
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA162652682
}}

{{PharmGKB
|RSID=rs9923231
|Name_s=VKORC1: -1639G>A
|Gene_s=VKORC1
|Feature=NA
|Evidence=PubMed ID:20203262
|Annotation=Risk or phenotype-associated allele: minor allele A was associated with decrease in warfarin dose requirements. Phenotype: In Asians, Blacks or Whites, this SNP (or equivalently, rs9934438 (1173C>T)) captures the variability in warfarin dose attributable to VKORC1. Study size/population/ethnicity: 1103 Asians, 670 Blacks, 3113 Whites. Type of association: CO; GN; PD
|Drugs=warfarin
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165291601
}}

{{omim
|id=608547
|rsnum=9923231
|variant=0006
}}

{{PMID Auto
|PMID=21179439
|Title=VKORC1 common variation and bone mineral density in the Third National Health and Nutrition Examination Survey
|OA=1
}}

{{PMID Auto
|PMID=22321278
|Title=[Impact of CYP2C9 and VKORC1 polymorphism on warfarin response during initiation of therapy]
}}

{{PMID Auto
|PMID=16270629
|Title=VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation.
}}

{{PMID Auto
|PMID=17048007
|Title=Association of warfarin dose with genes involved in its action and metabolism.
|OA=1
}}

{{PMID Auto
|PMID=17387222
|Title=Genetic-based dosing in orthopedic patients beginning warfarin therapy.
|OA=1
}}

{{PMID Auto
|PMID=17635701
|Title=VKORC1: molecular target of coumarins.
}}

{{PMID Auto
|PMID=18252229
|Title=Warfarin pharmacogenetics: CYP2C9 and VKORC1 genotypes predict different sensitivity and resistance frequencies in the Ashkenazi and Sephardi Jewish populations.
|OA=1
}}

{{PMID Auto
|PMID=18305455
|Title=Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin.
|OA=1
}}

{{PMID Auto
|PMID=18466099
|Title=Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans.
|OA=1
}}

{{PMID Auto
|PMID=18559094
|Title=Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction.
|OA=1
}}

{{PMID Auto
|PMID=18574025
|Title=The largest prospective warfarin-treated cohort supports genetic forecasting.
|OA=1
}}

{{PMID Auto
|PMID=18596683
|Title=Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.
|OA=1
}}

{{PMID Auto
|PMID=18662264
|Title=Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patients.
|OA=1
}}

{{PMID Auto
|PMID=18680736
|Title=Genetic factors contribute to patient-specific warfarin dose for Han Chinese.
}}

{{PMID Auto
|PMID=18752379
|Title=Warfarin pharmacogenetics.
|OA=1
}}

{{PMID Auto
|PMID=18809808
|Title=Ethnic differences in cardiovascular drug response: potential contribution of pharmacogenetics.
|OA=1
}}

{{PMID Auto
|PMID=18855533
|Title=VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans.
|OA=1
}}

{{PMID Auto
|PMID=19074728
|Title=Relative contribution of CYP2C9 and VKORC1 genotypes and early INR response to the prediction of warfarin sensitivity during initiation of therapy.
|OA=1
}}

{{PMID Auto
|PMID=19538716
|Title=Thrombotic genetic risk factors and warfarin pharmacogenetic variants in Sao Miguel's healthy population (Azores).
|OA=1
}}

{{PMID Auto
|PMID=19875892
|Title=A vitamin K epoxide reductase-oxidase complex gene polymorphism (-1639G>A) and interindividual variability in the dose-effect of vitamin K antagonists.
}}

{{PMID Auto
|PMID=19955245
|Title=Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.
|OA=1
}}

{{PMID Auto
|PMID=20017677
|Title=ARMS test for diagnosis of CYP2C9 and VKORC1 mutation in patients with pulmonary embolism in Han Chinese.
}}

{{PMID Auto
|PMID=20149073
|Title=Pharmacogenetics of acenocoumarol in patients with extreme dose requirements.
}}

{{PMID Auto
|PMID=20193673
|Title=Genotype polymorphisms of GGCX, NQO1, and VKORC1 genes associated with risk susceptibility in patients with large-artery atherosclerotic stroke.
}}

{{PMID Auto
|PMID=20585445
|Title=A novel, single algorithm approach to predict acenocoumarol dose based on CYP2C9 and VKORC1 allele variants.
|OA=1
}}

{{PMID Auto
|PMID=20733952
|Title=Warfarin genotyping using three different platforms.
|OA=1
}}

{{PMID Auto
|PMID=22010099
|Title=VKORC1 and CYP2C9 genotype and patient characteristics explain a large proportion of the variability in warfarin dose requirement among children.
}}

{{PMID Auto
|PMID=22178823
|Title=[Distribution of variant alleles association with warfarin pharmacokinetics and pharmacodynamics in the Han population in China].
}}

{{PMID Auto
|PMID=22486182
|Title=Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients.
}}

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs9923231
|overall_frequency_n=44
|overall_frequency_d=128
|overall_frequency=0.34375
|n_genomes=24
|n_genomes_annotated=0
|n_haplomes=39
|n_articles=3
|n_articles_annotated=1
|in_gwas=Y
|in_pharmgkb=Y
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=23124848
|Title=SNPs in VKORC1 are risk factors for systemic lupus erythematosus in asians
|OA=1
}}

{{PMID Auto
|PMID=23473641
|Title=Effect of CYP2C9 and VKORC1 genetic polymorphisms on mean daily maintenance dose of acenocoumarol in South Indian patients
}}

{{PMID Auto
|PMID=23104259
|Title=Influence of warfarin dose-associated genotypes on the risk of hemorrhagic complications in Chinese patients on warfarin
}}

{{PMID Auto
|PMID=23662025
|Title=Genetic variation and haplotype structure of the gene Vitamin K epoxide reductase complex, subunit 1 in the Tamilian population
|OA=1
}}

{{PMID Auto
|PMID=23732872
|Title=Association of VKORC1-1639G&gt;A polymorphism with susceptibility to ossification of the posterior longitudinal ligament of the spine: a Korean study
}}

{{PMID Auto
|PMID=23835662
|Title=Pharmacogenomics, ancestry and clinical decision making for global populations
}}

{{PMID Auto
|PMID=22592842
|Title=Oral anticoagulation and VKORC1 polymorphism in patients with a mechanical heart prosthesis: a 6-year follow-up.
}}

{{PMID Auto
|PMID=22676711
|Title=Pharmacogenomics of warfarin in populations of African descent.
|OA=1
}}

{{PMID Auto
|PMID=23133420
|Title=Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin.
|OA=1
}}

{{PMID Auto
|PMID=23691226
|Title=Novel associations of VKORC1 variants with higher acenocoumarol requirements.
|OA=1
}}

{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}