CYP4F2 rs2108622: What Your Genotype Means
The rs2108622 variant is a genetic change in the CYP4F2 gene that results in a substitution of the amino acid valine with methionine at position 433. This variant is associated with altered vitamin K metabolism and has been shown to influence the maintenance dose of the anticoagulant medication warfarin.
What each genotype means
Lower warfarin dose requirement
This genotype is associated with a lower maintenance dose requirement for the anticoagulant medication warfarin compared to those carrying the T allele. Research suggests that individuals with this profile may require less medication to achieve therapeutic anticoagulation. Please discuss your specific dosing needs and any medication management with your clinician or pharmacist.
This is a common genotype found in many populations, though frequencies vary significantly by ancestry.
Intermediate warfarin dose requirement
This genotype represents a heterozygous state that typically results in an intermediate warfarin dose requirement compared to the C/C and T/T genotypes. The influence of this variant on your medication needs is part of a broader genetic profile that includes other genes like VKORC1 and CYP2C9. Please consult your healthcare provider to determine how this information should be integrated into your personalized treatment plan.
This genotype is frequently observed in populations of European ancestry, where the T allele is present in approximately 25-30% of individuals.
Higher warfarin dose requirement
This genotype is associated with a higher maintenance dose requirement for warfarin compared to individuals carrying the C allele. Studies indicate that each T allele may contribute to an increase in the required weekly dose of the medication. Because warfarin dosing is complex and depends on multiple genetic and clinical factors, please work closely with your doctor or pharmacist to manage your dosage safely.
This genotype is less common than the C/C or C/T genotypes in many populations, occurring in a smaller subset of individuals of European ancestry.
Understanding the rs2108622 Variant
The rs2108622 variant, often referred to as the V433M polymorphism, is a single nucleotide polymorphism (SNP) located within the CYP4F2 gene. In this specific genetic change, a cytosine (C) is replaced by a thymine (T) at a specific position in the DNA sequence. This alteration leads to a missense mutation where the amino acid valine is replaced by methionine in the resulting protein. While this change does not typically affect the transcription of mRNA, research suggests it may lead to decreased levels of the CYP4F2 protein, potentially due to changes in protein translation or degradation rates. This variant is a primary focus in pharmacogenomics because of its documented role in how the body processes certain substances, most notably vitamin K, which in turn affects the body's response to blood-thinning medications.
The Role of the CYP4F2 Gene
The CYP4F2 gene provides instructions for making an enzyme that belongs to the cytochrome P450 family. These enzymes are primarily responsible for metabolizing various compounds, including drugs and endogenous substances. A critical function of the CYP4F2 enzyme is its role as a vitamin K1 oxidase. Vitamin K is essential for the body's blood-clotting process. By oxidizing vitamin K, the CYP4F2 enzyme helps regulate the levels of this vitamin in the liver. When the V433M variant is present, the enzyme's capacity to metabolize vitamin K1 is reduced. This reduction can lead to higher levels of vitamin K1 in the liver, which counteracts the effects of warfarin. Because warfarin works by inhibiting the recycling of vitamin K to prevent clotting, individuals with this variant may require a different dosage to achieve the same therapeutic effect.
Research and Clinical Associations
Extensive research has investigated the link between the rs2108622 variant and warfarin dosing. Studies have consistently observed that individuals carrying the T allele (the variant allele) often require a higher maintenance dose of warfarin compared to those with the CC genotype. This association is particularly well-documented in European populations. However, the strength and clinical relevance of this association can vary significantly based on ancestry. For instance, some studies have found that the impact of this variant on warfarin dosing is less pronounced or not statistically significant in African American populations. It is important to note that warfarin dosing is complex and influenced by multiple genetic factors, including variants in the VKORC1 and CYP2C9 genes, as well as clinical factors like age and body weight. Therefore, this SNP is considered one piece of a larger puzzle in personalized medicine.
Population Frequency
The frequency of the rs2108622 variant varies significantly across different ancestral groups. In European populations, the minor allele frequency is approximately 25% to 30%. In contrast, the frequency is notably lower in other populations, such as African Americans, where it has been observed at approximately 8%. These differences highlight the importance of considering ancestry when interpreting genetic data in a clinical context.
What This Information Means for You
If you are aware of your genotype for rs2108622, it is essential to understand that this information is for educational purposes only and should not be used to make personal medical decisions. Genetic variants are only one factor that clinicians consider when determining the appropriate dose of a medication like warfarin. Other factors, including your medical history, current medications, and other genetic markers, play a critical role. You should never adjust your medication dosage based on genetic test results without consulting your healthcare provider or pharmacist. They are the only ones qualified to interpret your genetic information in the context of your overall health and to determine if a dosage adjustment is necessary or safe for you.
How common is this variant?
The minor allele frequency for rs2108622 is approximately 25-30% in European populations, while it is significantly lower in other groups, such as African Americans, at approximately 8%.
Frequently asked questions
Does the rs2108622 variant mean I will have trouble with warfarin?
Not necessarily. While this variant is associated with a need for higher warfarin doses in some people, it is only one of many factors that influence how your body responds to the drug. Your doctor will consider your overall health, other medications, and additional genetic markers before determining your dose.
Should I get tested for the CYP4F2 variant?
Genetic testing for warfarin sensitivity is sometimes used in clinical settings, but it is not required for everyone. You should discuss with your doctor whether such testing is appropriate for your specific medical situation.
Can I change my diet to compensate for this genotype?
Warfarin dosing is highly sensitive to dietary vitamin K intake. Regardless of your genotype, it is important to maintain a consistent intake of vitamin K-rich foods and discuss any major dietary changes with your healthcare provider.
Is this variant associated with any other health conditions?
The primary clinical association for rs2108622 is its role in vitamin K metabolism and its impact on warfarin dosing. While research continues into other potential roles for the CYP4F2 enzyme, its primary clinical relevance remains in the field of pharmacogenomics.
Sources & further reading
Educational information only, last refreshed 9/16/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Functional CYP4F2 variant influencing vitamin K metabolism and clinical warfarin dose requirements.
Coding variant c.1297C>T (p.Arg433Trp) in CYP4F2. Note: The primary clinical variant for warfarin dosing in CYP4F2 is rs2108622 (c.1347C>T); rs72552769 is a distinct, rare variant.
This variant (V433M, *3 allele) decreases vitamin K metabolism, typically requiring an increased maintenance dose of warfarin to achieve target anticoagulation.