VKORC1 rs2359612: Understanding Warfarin Sensitivity Markers
The rs2359612 variant is a genetic marker located within the VKORC1 gene, which plays a critical role in the body's response to the anticoagulant medication warfarin. Research indicates that variations in this gene are significant factors in determining the dosage requirements for patients undergoing anticoagulant therapy.
What each genotype means
Higher warfarin dose requirement
This genotype is associated with higher warfarin dose requirements compared to carriers of the T allele. Research indicates that VKORC1 variants are major determinants of warfarin sensitivity, and you should discuss your specific dosing needs with your clinician or pharmacist.
This genotype is common in many populations, though frequencies vary significantly by ancestry.
Intermediate warfarin dose requirement
This genotype represents an intermediate state regarding warfarin sensitivity. Because VKORC1 variants significantly influence how much warfarin is needed to achieve a target INR, please consult your healthcare provider to determine if your genotype should be considered in your dosing plan.
This heterozygous genotype is frequently observed across diverse global populations.
Lower warfarin dose requirement
This genotype is often associated with increased sensitivity to warfarin, which may necessitate lower starting doses to reach therapeutic targets safely. As VKORC1 is a primary genetic factor in warfarin response, always coordinate with your clinician or pharmacist regarding your medication management.
This genotype is common in many populations, with prevalence rates that differ by ethnic background.
What is rs2359612 and Where is it Located?
The variant rs2359612 is a single nucleotide polymorphism (SNP) situated within the VKORC1 gene, which is located on chromosome 16 at position 16p11.2. In the context of human genetics, a SNP represents a variation at a single position in the DNA sequence among individuals. This specific variant is one of several markers within the VKORC1 gene that researchers track to understand how genetic diversity influences drug metabolism. Because it is located in a non-coding region of the gene, its primary influence is thought to be mediated through the regulation of VKORC1 protein expression rather than by altering the structure of the protein itself. Scientists study this marker as part of broader haplotype analyses to better predict how different individuals might process medications that target this specific biological pathway.
The Role of the VKORC1 Gene
The VKORC1 gene provides instructions for making the vitamin K epoxide reductase complex subunit 1 enzyme. This enzyme is essential for the vitamin K cycle, a process that allows the body to recycle vitamin K, which is necessary for the production of functional blood-clotting factors. Warfarin, a commonly prescribed anticoagulant, works by inhibiting this enzyme, thereby reducing the body's ability to form blood clots. Because VKORC1 is the direct pharmacological target of warfarin, any genetic variation that changes the expression levels or efficiency of this enzyme can significantly alter how sensitive a patient is to the drug. Understanding these genetic differences is a cornerstone of pharmacogenomics, the field of study that examines how an individual's genetic makeup affects their response to drugs.
Research Associations and Evidence Strength
The evidence linking VKORC1 variants to warfarin dosing is considered robust, with rs2359612 frequently included in studies and clinical algorithms alongside other markers like rs9923231. Research has consistently shown that specific genotypes at these loci are associated with variations in the dose of warfarin required to achieve a therapeutic effect. For instance, patients with certain genotypes may require lower doses to avoid excessive bleeding, while others may require higher doses to achieve the desired anticoagulant effect. While the evidence for the influence of VKORC1 on warfarin dosing is strong, it is important to note that dosing is multifactorial. Clinical algorithms often incorporate age, weight, and other genetic markers, such as those in the CYP2C9 gene, to provide a comprehensive picture of a patient's likely response to the medication.
Clinical Implications and Patient Guidance
It is vital to understand that genetic information regarding rs2359612 is intended for educational and research purposes and should never be used to self-diagnose or adjust medication. Pharmacogenomic markers are tools used by clinicians to help personalize treatment plans, but they are only one piece of a complex clinical puzzle. If you are taking warfarin or are scheduled to begin anticoagulant therapy, you should discuss your genetic profile with your healthcare provider or a clinical pharmacist. They are the only professionals qualified to interpret these results in the context of your overall health, medical history, and other medications you may be taking. Never change your dosage or stop taking prescribed medication based on genetic test results without direct supervision from your medical team.
How common is this variant?
The rs2359612 variant is common, with a Global Minor Allele Frequency (GMAF) of approximately 0.4986. Its frequency can vary significantly across different ancestral populations, which is a key consideration in pharmacogenomic research.
Frequently asked questions
Does my rs2359612 genotype mean I need a different warfarin dose?
Genetic variants in VKORC1 are known to influence warfarin sensitivity, but they are only one factor in determining the correct dose. Your doctor will consider your age, weight, diet, and other genetic markers like CYP2C9 to determine the safest and most effective dose for you.
Can I use this genetic information to change my medication?
No. You should never change your medication dosage or schedule based on genetic test results. Any adjustments to your treatment must be made exclusively by your healthcare provider.
Is VKORC1 the only gene that affects warfarin?
No, warfarin response is complex. Other genes, particularly CYP2C9, play a major role in how the body metabolizes the drug. Clinical dosing algorithms typically account for multiple genetic and non-genetic factors.
Where can I find more information about pharmacogenomics?
You can find reliable information through resources like MedlinePlus Genetics or the Pharmacogenomics Knowledge Base (PharmGKB). These sites provide educational materials on how genes influence drug response.
Sources & further reading
Educational information only, last refreshed 10/1/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs2359612?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in VKORC1
The VKORC1 -1639G>A promoter variant reduces vitamin K epoxide reductase subunit 1 expression, requiring lower therapeutic warfarin maintenance doses to prevent bleeding complications.
This VKORC1 variant is a clinically useful marker for sensitivity to warfarin and related vitamin-K-antagonist dosing, with direct implications for medication safety.
Promoter variant in VKORC1 influencing warfarin sensitivity and dosing requirements.
Regulatory variant in the VKORC1 promoter region that significantly influences warfarin dose requirements.
Located in VKORC1, this missense variant (p.Val66Met) is associated with warfarin resistance requiring elevated therapeutic dosages.
Intronic regulatory variant in VKORC1 in high linkage disequilibrium with rs9923231, dictating clinical warfarin dosing requirements.