From SNPedia
| Geno
|
Mag
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Summary
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| (C;C)
|
0
|
normal
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| (C;T)
|
2
|
reduced warfarin dose if treated for VTE
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| (T;T)
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2.1
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reduced warfarin dose if treated for VTE
|
| ? | (C;C) (C;T) (T;T) | 28 |
|---|
 |
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]
| OMIM | 608547 |
| Desc | VITAMIN K EPOXIDE REDUCTASE COMPLEX, SUBUNIT 1; VKORC1 |
| Variant | |
| Related | also |
| GWAS snp
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| PMID
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[PMID 19300499]
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| Trait
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Warfarin maintenance dose
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| Title
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A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose
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| Risk Allele
|
T
|
| P-val
|
0
|
| Odds Ratio
|
0.97 [0.91-1.02] mg/week decrease
|
| PharmGKB | PA165111643 |
| Name | upstream -1639G>A |
| 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 ± 1.2 mg (−50%) for AA homozygotes, 2.8 ± 1.3 mg (−26%) for GA heterozygotes, 3.8 ± 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. |
| Gene | VKORC1 |
| Featue | NA |
| Evidence | PubMed ID:19794411 |
| Drugs | warfarin |
| Diseases | |
| Curation Level | Curated |
[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
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| PMID
|
[PMID 20833655]
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| Trait
|
|
| Title
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Genome-wide association study identifies genetic determinants of warfarin responsiveness for Japanese
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| Risk Allele
|
|
| P-val
|
9E-31
|
| Odds Ratio
|
None None
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| PharmGKB | PA161748415 |
| Name | VKORC1:-1639 |
| Annotation | In a GWAS study, this SNP was strongly associated with stabilized warfarin dose, and was in perfect linkage disequilibrium with rs10871454. |
| Gene | VKORC1 |
| Featue | NA |
| Evidence | PubMed ID:18535201 |
| Drugs | warfarin |
| Diseases | |
| Curation Level | Curated |
| PharmGKB | PA164739914 |
| Name | |
| 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. |
| Gene | VKORC1 |
| Featue | NA |
| Evidence | PubMed ID:19300499; Web Resource:http://www.genome.gov/gwastudies/ |
| Drugs | warfarin |
| Diseases | |
| Curation Level | Non-Curated |
| PharmGKB | PA162652682 |
| Name | VKORC1:G3673A, VKORC1:-1639G>A |
| 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. |
| Gene | VKORC1 |
| Featue | NA |
| Evidence | PubMed ID:19228618 |
| Drugs | warfarin |
| Diseases | |
| Curation Level | Curated |
| PharmGKB | PA165291601 |
| Name | VKORC1: -1639G>A |
| 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 |
| Gene | VKORC1 |
| Featue | NA |
| Evidence | PubMed ID:20203262 |
| Drugs | warfarin |
| Diseases | |
| Curation Level | Curated |
[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]
