CYP2C9 rs28371685: What Your Genotype Means
The rs28371685 variant is a genetic change in the CYP2C9 gene that defines the *11 allele. This variant is associated with decreased metabolic activity, which may influence how the body processes certain medications, including warfarin.
What each genotype means
Normal enzyme activity
This genotype represents the most common form of the CYP2C9 gene, often referred to as the *1 allele. Individuals with this profile typically possess standard metabolic activity for drugs processed by this enzyme, such as warfarin and certain NSAIDs. Please discuss any medication dosing or concerns with your healthcare provider or pharmacist.
This is the most common genotype found across all global populations.
Reduced enzyme activity
This genotype indicates you carry one copy of the CYP2C9*11 variant, which is associated with decreased metabolic activity for certain medications. Research suggests that individuals with this variant may process drugs like warfarin or NSAIDs more slowly than those without it. You should consult with your clinician or pharmacist regarding how this may influence your medication dosing or safety.
This genotype is primarily observed in individuals of African ancestry and is rare or absent in European and Asian populations.
Significantly reduced enzyme activity
This genotype indicates you carry two copies of the CYP2C9*11 variant, which is linked to a more pronounced reduction in the enzyme's ability to metabolize specific drugs. Because this may lead to higher drug levels in your system, it is important to discuss this genetic finding with your doctor or pharmacist before starting medications metabolized by CYP2C9. They can help determine if dose adjustments are necessary for your safety.
This genotype is very uncommon and is found almost exclusively in populations of African ancestry.
Understanding the rs28371685 Variant
The rs28371685 variant is a specific single nucleotide polymorphism (SNP) located within the CYP2C9 gene. In scientific literature, this variant is commonly referred to as the CYP2C9*11 allele. It involves a change in the DNA sequence that results in an amino acid substitution (p.Arg335Trp) within the protein structure. This change is categorized as a missense variant, meaning it alters the genetic code to produce a slightly different version of the enzyme. Because the CYP2C9 enzyme is responsible for breaking down many common drugs, variations like rs28371685 can change how efficiently these medications are cleared from the bloodstream. Researchers study this variant to understand why individuals may experience different responses to standard drug doses.
The Role of the CYP2C9 Gene
The CYP2C9 gene provides instructions for making an enzyme that belongs to the cytochrome P450 family. These enzymes are primarily found in the liver and are essential for the metabolism of a wide variety of substances, including toxins and therapeutic drugs. CYP2C9 is particularly well-known for its role in metabolizing warfarin, a common anticoagulant used to prevent blood clots, as well as various nonsteroidal anti-inflammatory drugs (NSAIDs). When the CYP2C9 enzyme functions normally, it helps maintain steady levels of these medications in the body. However, when genetic variants like rs28371685 reduce the enzyme's activity, the body may process these drugs more slowly. This can lead to higher concentrations of the medication in the blood, which may increase the risk of side effects if the dosage is not adjusted appropriately.
Research and Clinical Evidence
Research into rs28371685 has primarily focused on its impact on drug metabolism, particularly for warfarin. Studies have consistently associated the *11 allele with decreased metabolic activity compared to the common, fully functional *1 allele. While the evidence linking this variant to altered drug metabolism is well-documented in laboratory settings, its clinical impact is often studied alongside other CYP2C9 variants. Because many clinical trials historically focused on European-ancestry populations—where this variant is rare—the evidence for its specific clinical effect size is sometimes described as limited or requiring further validation in diverse cohorts. Current pharmacogenomic guidelines emphasize that clinicians should consider an individual's full genetic profile when determining dosages for drugs metabolized by this enzyme, as multiple variants can collectively influence a patient's metabolic status.
Population Frequency
The distribution of the rs28371685 variant is highly dependent on ancestry. It is most frequently observed in populations of African ancestry, where it is considered a clinically relevant allele. In contrast, this variant is virtually absent in populations of European or Asian descent. Because of this, genetic screening programs that only test for common European-associated variants may miss this allele, potentially leading to an incomplete picture of a patient's metabolic capacity. Understanding these ancestry-specific differences is a major focus of modern pharmacogenomics, as it helps ensure that medical guidelines are equitable and effective for all patients regardless of their genetic background.
Managing Your Genetic Information
If you have information about your CYP2C9 genotype, it is important to understand that this data is only one piece of a larger clinical puzzle. Genetic variants do not act in isolation; factors such as age, weight, diet, other medications, and liver function also play significant roles in how your body processes drugs. You should never use genetic information to make changes to your medication regimen on your own. If you are concerned about how your genetics might affect your response to a prescribed drug, the best course of action is to discuss your results with your healthcare provider or a clinical pharmacist. They can interpret your genetic data in the context of your overall health and determine if a dosage adjustment or alternative therapy is appropriate for you.
How common is this variant?
The rs28371685 variant has a minor allele frequency of approximately 0.01 in African-ancestry populations and is virtually absent in European and Asian populations.
Frequently asked questions
Does having the rs28371685 variant mean I cannot take warfarin?
No, having this variant does not mean you cannot take warfarin. It simply means your body may process the medication more slowly, which your doctor can account for by adjusting your dose or monitoring your blood levels more closely.
Should I get tested for CYP2C9 variants?
Genetic testing for CYP2C9 is typically ordered by a physician when starting medications like warfarin to help guide initial dosing. You should discuss with your doctor whether testing is appropriate for your specific medical situation.
Is rs28371685 the only variant that affects CYP2C9?
No, the CYP2C9 gene is highly polymorphic, meaning there are many different variants that can affect its function. Other common variants include *2, *3, *5, *6, and *8, all of which can influence how the enzyme works.
Can I change my CYP2C9 genotype?
No, your genotype is inherited from your parents and remains the same throughout your life. It is a permanent part of your biological makeup.
Sources & further reading
Educational information only, last refreshed 9/19/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in CYP2C9
Rare variant in the CYP2C9 gene potentially impacting enzyme activity and drug metabolism; clinical significance requires further validation.
Coding variant conferring the CYP2C9*3 allele (often mislabeled as *4 in older literature) with decreased enzymatic activity affecting clearance of drugs such as warfarin and phenytoin.
Missense mutation defining the CYP2C9*5 allele that dramatically lowers metabolic activity towards oral anticoagulants and anti-epileptic medications.
A rare variant in the CYP2C9 gene that may impact the metabolism of various clinical drugs.
The CYP2C9*2 variant (p.Arg144Cys) results in reduced enzymatic activity, significantly impacting the metabolism and required dosing of substrates such as warfarin and irbesartan.
Defining the CYP2C9*3 (p.Ile359Leu) allele, this variant markedly decreases enzymatic activity, requiring reduced dosages for warfarin and phenytoin to prevent toxicity.