CYP2C9 rs28399507: What Your Genotype Means
The rs28399507 variant is a specific genetic change located within the CYP2C9 gene. It is primarily recognized as a marker for the CYP2C9*8 allele, which is associated with reduced enzyme activity and may influence how an individual metabolizes medications like warfarin.
What each genotype means
Normal enzyme activity
This genotype represents the reference state for this position in the CYP2C9 gene. Individuals with this genotype are typically considered to have normal enzyme function regarding this specific variant. Please discuss your medication dosing requirements with your clinician or pharmacist.
This is the most common genotype in most global populations.
Decreased enzyme activity
This genotype includes one copy of the variant allele associated with the CYP2C9*8 decreased-function allele. Research indicates this may lead to lower warfarin dose requirements, particularly in individuals of African ancestry. Please discuss your medication dosing requirements with your clinician or pharmacist.
This genotype is observed primarily in populations of African ancestry, with a minor allele frequency of approximately 0.05.
Reduced enzyme activity
This genotype indicates you carry two copies of the variant allele associated with the CYP2C9*8 decreased-function allele. This is linked to reduced metabolism of certain drugs, including warfarin, which may necessitate lower dose requirements. Please discuss your medication dosing requirements with your clinician or pharmacist.
This genotype is rare and found primarily in individuals of African ancestry.
Understanding the Variant and Its Location
The rs28399507 variant is a single nucleotide polymorphism (SNP) situated within the CYP2C9 gene on chromosome 10. This gene provides instructions for creating an enzyme that belongs to the cytochrome P450 family, a group of proteins essential for processing various substances in the body. In the context of genomics, rs28399507 serves as a key identifier for the CYP2C9*8 allele. Because this variant is located in a region of the genome responsible for drug metabolism, researchers study it to understand how genetic differences contribute to the wide variation in how people respond to certain pharmaceutical treatments. It is important to note that while this SNP is a useful marker, it is part of a complex genetic landscape where multiple variants across the CYP2C9 gene can influence overall enzyme function.
The Role of the CYP2C9 Gene
The CYP2C9 gene encodes an enzyme that plays a critical role in the metabolism of many common medications, including phenytoin, ibuprofen, and the anticoagulant warfarin. This enzyme is primarily active in the liver, where it helps break down these drugs into forms that the body can eliminate. When the CYP2C9 gene functions normally, the enzyme processes these drugs at a predictable rate. However, genetic variations can lead to changes in the enzyme's structure or expression levels. Some variants, such as those identified by rs28399507, are associated with decreased enzyme activity. When an individual has reduced CYP2C9 function, their body may process certain medications more slowly than expected. This can lead to higher concentrations of the drug in the bloodstream, which is a significant consideration for clinicians when determining appropriate starting doses for drugs with a narrow therapeutic index, such as warfarin.
Research and Clinical Evidence
Research into rs28399507 has primarily focused on its role in pharmacogenomics, specifically regarding warfarin therapy. Studies have observed that individuals carrying the CYP2C9*8 allele, identified by this variant, may require lower doses of warfarin to achieve the desired therapeutic effect compared to those with the most common, fully functional enzyme. The evidence for this association is considered limited but clinically relevant, particularly in populations where this allele is more common. While genetic testing can provide insights into potential drug metabolism, it is not the only factor that determines a patient's response to medication. Other variables, such as age, body weight, diet, and the presence of other genetic variants like those in the VKORC1 gene, also play major roles. Consequently, clinicians use validated dosing algorithms that incorporate both genetic and clinical data to guide treatment decisions rather than relying on a single genetic marker.
Navigating Your Genetic Information
If you have received information about your rs28399507 genotype, it is essential to understand that this data is for educational purposes and does not constitute a medical diagnosis. Genetic variants are only one piece of a much larger puzzle regarding how your body interacts with medications. You should never change your medication dosage or stop taking a prescribed drug based on genetic test results without first consulting your healthcare provider. Your doctor or pharmacist is the best resource for interpreting how your specific genetic profile might influence your treatment plan. They can combine your genetic information with your clinical history to ensure that your medication regimen is safe and effective. If you are concerned about how your genetics might affect your response to a specific drug, bring your report to your next appointment to discuss it with your clinical team.
How common is this variant?
The rs28399507 variant is most prevalent in populations of African ancestry, with a minor allele frequency of approximately 0.05.
Frequently asked questions
What does it mean to have a decreased-function CYP2C9 allele?
Having a decreased-function allele means your liver may produce an enzyme that processes certain medications more slowly than average. This can lead to higher levels of the drug in your system, which may require your doctor to adjust your dosage.
Does this variant mean I cannot take warfarin?
No, this variant does not mean you cannot take warfarin. It simply means that your genetic profile is one of many factors your doctor will consider when determining the safest and most effective dose for you.
Should I get tested for rs28399507?
Genetic testing for pharmacogenomics is typically ordered by a physician when it is clinically indicated for specific medications. You should discuss with your doctor whether such testing is appropriate for your specific health situation.
Is rs28399507 the only variant that affects warfarin?
No, warfarin response is complex and influenced by multiple genes, including VKORC1 and other variants within the CYP2C9 gene. Clinicians often use algorithms that account for these multiple genetic and clinical factors.
Sources & further reading
Educational information only, last refreshed 9/17/2026. 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.