What you carry at this position in your DNA and what research says about it.
Cardiovascular Risk: 8/10 evidence, 31 publications.
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Sample genotype (not yours): A/A
Lower Cardiovascular Risk and High Warfarin Sensitivity
Lower risk of stroke and heart disease in East Asian populations characterizes this genetic profile. It also indicates high sensitivity to warfarin, meaning it produces a stronger effect, with a greater bleeding risk.
What this genotype means: Lower risk of stroke and coronary heart disease; High sensitivity to warfarin therapy.
Sample genotype (not yours): A/G
Increased Cardiovascular Risk and Moderate Warfarin Sensitivity
Increased risk of stroke and heart disease in East Asian populations is associated with this genetic profile. It also indicates moderate sensitivity to warfarin, with a stronger effect at a given amount than average.
What this genotype means: Elevated risk of stroke and coronary heart disease; Moderate sensitivity to warfarin therapy.
Sample genotype (not yours): G/G
Increased Cardiovascular Risk and Typical Warfarin Sensitivity
Increased risk of stroke and heart disease in East Asian populations is associated with this genetic profile. It also indicates typical sensitivity to warfarin, meaning a typical response is expected.
What this genotype means: Elevated risk of stroke and coronary heart disease; Typical sensitivity to warfarin therapy.
Gene function and biological role
Gene Function: VKORC1 encodes the vitamin K epoxide reductase complex subunit 1, a critical enzyme in the vitamin K cycle [1]. This enzyme is responsible for converting vitamin K epoxide back into its active, reduced form [1]. Active vitamin K is essential for the gamma-carboxylation of clotting factors and other proteins like osteocalcin and matrix Gla protein [2]. Consequently, VKORC1 plays a central role in both blood coagulation and calcium metabolism [2]. It is also the primary therapeutic target of oral anticoagulants like warfarin [3].
Variant Impact: Located within the VKORC1 gene, rs2359612 is an intronic single nucleotide polymorphism [4]. This genetic change is in strong linkage disequilibrium with other key regulatory variants, such as rs9923231 [5]. It significantly influences the expression levels of the VKORC1 enzyme, thereby altering vitamin K recycling efficiency [3]. Additionally, the variant has been associated with differences in vascular calcification and cardiovascular disease susceptibility [7].
Key Insight: This variant is part of a major genetic haplotype that determines up to one-third of the individual variation in warfarin response.
Location: VKORC1. Chromosome 16 · 16p11.2 · 31.1 Mb
Estimated prevalence by population
Global 14.1%; European 14.3%; African 4.3%; East Asian 79.6%; South Asian 3.2%; Americas 16.3%; Ashkenazi 25.7%; Finnish 15.3%; Middle Eastern 28.9%; Amish 19.6%.
Estimated AA genotype frequency.
Global 41.9%; European 47.0%; African 33.0%; East Asian 19.3%; South Asian 29.4%; Americas 48.2%; Ashkenazi 50.0%; Finnish 47.6%; Middle Eastern 49.7%; Amish 49.3%.
Estimated AG genotype frequency.
Global 44.0%; European 38.7%; African 62.7%; East Asian 1.2%; South Asian 67.4%; Americas 35.5%; Ashkenazi 24.3%; Finnish 37.1%; Middle Eastern 21.4%; Amish 31.1%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Cardiovascular & Metabolic
Heart Disease
Cardiovascular Risk. Evidence: 3/10. Source: PMID 18841283. Lower Risk.
Pharmacogenomics
Anticoagulant & Blood Thinner Response
Warfarin Sensitivity. Evidence: 8/10. Source: PMID 15883587. High Sensitivity.
Phenprocoumon Response. Evidence: 5/10. Source: PMID 19738376. Stronger Response.
Organ Systems
Bone, Joint & Connective Tissue Health
Osteocalcin Levels. Evidence: 6/10. Source: PMID 39789286. Typical Levels.
Showing effects for A/G genotype
Cardiovascular Risk. Evidence: 3/10. Source: PMID 18841283. Increased Risk.
Warfarin Sensitivity. Evidence: 8/10. Source: PMID 15883587. Moderate Sensitivity.
Osteocalcin Levels. Evidence: 6/10. Source: PMID 39789286. Slightly Higher.
Showing effects for G/G genotype
Warfarin Sensitivity. Evidence: 8/10. Source: PMID 15883587. Typical Sensitivity.
Phenprocoumon Response. Evidence: 5/10. Source: PMID 19738376. Typical Response.
Osteocalcin Levels. Evidence: 6/10. Source: PMID 39789286. Higher Levels.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Two copies of the A allele are linked to reduced expression of the VKORC1 enzyme [1]. This lower expression results in a lower baseline level of active vitamin K-dependent clotting factors [2]. Consequently, individuals with this genotype are highly sensitive to vitamin K antagonists like warfarin, so the drug produces a much stronger effect at a given amount [3]. Standard doses of warfarin in these individuals can lead to excessive anticoagulation and an increased risk of bleeding complications [4]. On the health front, this genotype is protective against vascular calcification and is associated with a lower risk of stroke and coronary heart disease, particularly in East Asian populations [5]. However, studies in European populations have shown mixed results regarding this cardiovascular association [6].
Lower risk of stroke and coronary heart disease; High sensitivity to warfarin therapy.
Sample genotype: AG (Heterozygous)
One copy of each allele results in intermediate VKORC1 enzyme expression [1]. This intermediate expression leads to moderate sensitivity to vitamin K antagonists like warfarin [2]. Clinical guidelines suggest that individuals with this genotype are typically more sensitive to warfarin than those with the G/G genotype, with a greater bleeding risk [3]. In terms of cardiovascular health, the presence of the G allele is associated with an increased risk of arterial vascular diseases, including stroke and coronary heart disease, especially in East Asian cohorts [4]. This is thought to be driven by higher rates of vascular calcification due to altered vitamin K cycle dynamics [5]. However, this association has not been consistently replicated in European populations, suggesting ethnic differences in risk [6].
Elevated risk of stroke and coronary heart disease; Moderate sensitivity to warfarin therapy.
Sample genotype: GG (Homozygous)
Two copies of the G allele are associated with higher expression of the VKORC1 enzyme [1]. This higher expression leads to typical or slightly resistant response to vitamin K antagonists like warfarin [2]. Individuals with this genotype generally respond less strongly to warfarin than carriers of the A allele [3]. On the cardiovascular side, this genotype is linked to an increased risk of stroke, coronary heart disease, and aortic dissection in East Asian populations [4]. The mechanism is believed to involve elevated VKORC1 activity promoting vascular calcification through altered carboxylation of calcium-regulating proteins [5]. In European populations, however, studies have not found a significant association between this genotype and stroke risk [6].
Elevated risk of stroke and coronary heart disease; Typical sensitivity to warfarin therapy.
Variants with shared genetic architecture
rs2884737 · VKORC1 Gene · Chr 16 · Warfarin Sensitivity
rs61742245 · VKORC1 Gene · Chr 16 · Warfarin Resistance
rs7294 · VKORC1 Gene · Chr 16 · Vitamin K and Bone Health
Association of warfarin dose with genes involved in its action and metabolism.
Common VKORC1 and GGCX polymorphisms associated with warfarin dose.
The largest prospective warfarin-treated cohort supports genetic forecasting.
Genetic determinants of response to warfarin during initial anticoagulation.
Content updated August 2026.
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