What you carry at this position in your DNA and what research says about it.
Blood Thinner Sensitivity: 8/10 evidence, 81 publications.
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Sample genotype (not yours): C/C
Typical Blood Thinner Sensitivity
You carry two copies of the common C allele, resulting in normal VKORC1 enzyme levels and typical vitamin K recycling. If prescribed blood thinners like warfarin, you are likely to show a typical response.
What this genotype means: Normal VKORC1 enzyme levels; Typical blood thinner response; Typical baseline risk for osteoporosis and lupus.
Sample genotype (not yours): C/T
Increased Blood Thinner Sensitivity
Carrying one copy of the T allele moderately reduces your VKORC1 enzyme levels. If prescribed warfarin or similar blood thinners, you are likely to be more sensitive to them, with a greater risk of bleeding.
What this genotype means: Moderately reduced VKORC1 enzyme levels; Greater sensitivity to warfarin and related anticoagulants; Slightly elevated risk of bleeding, osteoporosis, and lupus.
Sample genotype (not yours): T/T
High Blood Thinner Sensitivity
Carrying two copies of the T allele significantly reduces your VKORC1 enzyme levels. You are highly sensitive to blood thinners like warfarin, with a greater risk of severe bleeding.
What this genotype means: Significantly reduced VKORC1 enzyme levels; Much greater sensitivity to warfarin and related anticoagulants; Elevated risk of bleeding, osteoporosis, and lupus.
Gene function and biological role
Gene Function: The VKORC1 gene encodes the vitamin K epoxide reductase complex subunit 1 enzyme, which plays a critical role in the vitamin K cycle. This enzyme is responsible for converting oxidized vitamin K back into its active, reduced form. Active vitamin K is an essential cofactor required for the chemical modification and activation of several key blood clotting proteins, as well as bone-regulatory proteins like osteocalcin. Because of its central role in coagulation, VKORC1 is the primary therapeutic target for coumarin-based oral anticoagulants such as warfarin. Variations in this gene directly alter how efficiently the body recycles vitamin K, which in turn dictates how sensitive a person is to blood-thinning medications.
Variant Impact: The rs9923231 variant is a single nucleotide change located in the promoter region of the VKORC1 gene, often referred to in literature as -1639G to A due to opposite-strand orientation. This genetic change directly alters the rate at which the VKORC1 gene is transcribed into messenger RNA. Specifically, the T allele disrupts a transcription factor binding site, which significantly reduces the expression of the VKORC1 enzyme. With fewer enzymes available to recycle vitamin K, individuals carrying the T allele have a lower baseline capacity for blood clotting and are highly sensitive to vitamin K antagonists. This single variant is widely recognized as one of the most important genetic predictors of therapeutic blood thinner dosing.
Key Insight: This single genetic variant explains up to thirty percent of the individual differences in warfarin response. Because vitamin K is also vital for bone health, this same variant that alters blood clotting also influences bone mineral density and osteoporosis risk.
Location: VKORC1. Chromosome 16 · 16p11.2 · 31.1 Mb
Estimated prevalence by population
Global 49.3%; European 38.7%; African 81.0%; East Asian 1.2%; South Asian 67.6%; Americas 37.0%; Ashkenazi 25.1%; Finnish 37.1%; Middle Eastern 21.7%; Amish 31.2%.
Estimated CC genotype frequency.
Global 37.7%; European 47.0%; African 18.0%; East Asian 19.3%; South Asian 29.3%; Americas 47.6%; Ashkenazi 50.0%; Finnish 47.6%; Middle Eastern 49.8%; Amish 49.3%.
Estimated CT genotype frequency.
Global 13.0%; European 14.3%; African 1.0%; East Asian 79.5%; South Asian 3.2%; Americas 15.3%; Ashkenazi 24.9%; Finnish 15.3%; Middle Eastern 28.5%; Amish 19.5%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Pharmacogenomics
Anticoagulant & Blood Thinner Response
Warfarin Sensitivity. Evidence: 8/10. Source: PMID 15888487. Typical Sensitivity.
Adverse Drug Reactions
NSAID Bleeding Risk. Evidence: 5/10. Source: PMID 36942299. Typical Risk.
Organ Systems
Bone, Joint & Connective Tissue Health
Osteoporosis. Evidence: 3/10. Source: PMID 21179439. Typical Risk.
Immunity & Inflammation
Autoimmune Diseases
Lupus. Evidence: 3/10. Source: PMID 23124848. Typical Risk.
Showing effects for C/T genotype
Warfarin Sensitivity. Evidence: 8/10. Source: PMID 15888487. Increased Sensitivity.
NSAID Bleeding Risk. Evidence: 5/10. Source: PMID 36942299. Increased Risk.
Osteoporosis. Evidence: 3/10. Source: PMID 21179439. Slightly Increased.
Lupus. Evidence: 3/10. Source: PMID 23124848. Slightly Increased.
Showing effects for T/T genotype
Warfarin Sensitivity. Evidence: 8/10. Source: PMID 15888487. High Sensitivity.
NSAID Bleeding Risk. Evidence: 5/10. Source: PMID 36942299. High Risk.
Osteoporosis. Evidence: 3/10. Source: PMID 21179439. Increased Risk.
Lupus. Evidence: 3/10. Source: PMID 23124848. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Having the C/C genotype means your body produces a normal amount of the VKORC1 enzyme, which keeps your vitamin K recycling system operating at baseline capacity. Because your clotting factors are fully activated, you do not have an inherited sensitivity to coumarin-based anticoagulants. If you ever require treatment with blood thinners like warfarin, phenprocoumon, or acenocoumarol, you are likely to respond less strongly than T allele carriers. Additionally, your normal vitamin K recycling supports the proper activation of osteocalcin, maintaining typical bone mineral density. You also do not carry the genetic risk associated with this variant for autoimmune conditions like systemic lupus erythematosus. Your risk of gastrointestinal bleeding when taking nonsteroidal anti-inflammatory drugs is also at the typical baseline.
Normal VKORC1 enzyme levels; Typical blood thinner response; Typical baseline risk for osteoporosis and lupus.
Sample genotype: CT (Heterozygous)
Having the C/T genotype means you carry one copy of the sensitive T allele, which moderately reduces the expression of the VKORC1 enzyme in your liver. This reduction limits your body's ability to recycle vitamin K, making you more sensitive to the effects of oral anticoagulants. If prescribed medications like warfarin, phenprocoumon, or acenocoumarol, you are likely to be more sensitive to them than average. Without the right medical supervision, this can increase your likelihood of over-anticoagulation and bleeding complications. Furthermore, the slight reduction in active vitamin K recycling may modestly affect bone-regulatory proteins, which has been linked to lower bone mineral density. This genotype is also associated with a slightly higher susceptibility to systemic lupus erythematosus, particularly in individuals of Asian descent. You may also have a slightly higher risk of gastrointestinal bleeding when using NSAIDs.
Moderately reduced VKORC1 enzyme levels; Greater sensitivity to warfarin and related anticoagulants; Slightly elevated risk of bleeding, osteoporosis, and lupus.
Sample genotype: TT (Homozygous)
Having the T/T genotype means you have two copies of the sensitive variant, resulting in a major reduction of VKORC1 enzyme expression. Because your vitamin K recycling pathway is highly restricted, your baseline clotting factor activation is lower, making you extremely sensitive to vitamin K antagonists. If you are ever treated with warfarin, phenprocoumon, or acenocoumarol, you are likely to be significantly more sensitive to them than typical patients, with a greater risk of severe bleeding. Standard starting doses of these medications could quickly lead to dangerous over-anticoagulation. Beyond medication response, the chronic reduction in active vitamin K recycling impairs the activation of bone proteins, which is associated with a higher risk of low bone mineral density and osteoporosis. Additionally, this genotype is linked to an increased risk of developing systemic lupus erythematosus in Asian populations. You also have an elevated risk of experiencing gastrointestinal bleeding, especially when taking NSAIDs.
Significantly reduced VKORC1 enzyme levels; Much greater sensitivity to warfarin and related anticoagulants; Elevated risk of bleeding, osteoporosis, and lupus.
Variants with shared genetic architecture
rs2359612 · VKORC1 Gene · Chr 16 · Cardiovascular Risk
rs2884737 · VKORC1 Gene · Chr 16 · Warfarin Sensitivity
rs61742245 · VKORC1 Gene · Chr 16 · Warfarin Resistance
Content updated August 2026.
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