CYP2B6 rs28399437: What Your Genotype Means
The rs28399437 variant is a specific genetic change in the CYP2B6 gene, which provides instructions for making an enzyme responsible for breaking down various medications. This variant, often referred to as part of the CYP2B6*5 allele, is studied for its potential to influence how efficiently the body clears certain drugs from the system.
What each genotype means
Typical enzyme activity
You carry two copies of the common reference allele at this position, indicating standard baseline CYP2B6 enzyme expression for this specific locus. Published research associates this genotype with expected metabolic clearance rates for medications broken down by CYP2B6, such as methadone and bupropion. Discuss your overall medication regimen and personal dosing needs directly with your clinician or pharmacist.
Carried by approximately 75% to 85% of individuals of European ancestry and more than 90% of individuals of African ancestry.
Moderately reduced clearance
You carry one copy of the T allele, which corresponds to the star-allele designation CYP2B6*5. Limited pharmacogenomic evidence suggests this genotype may result in modestly reduced enzyme function and slower clearance of substrates like methadone or bupropion. Always consult your healthcare provider or pharmacist before making any changes to your medication doses.
Found in roughly 15% to 25% of individuals of European descent and about 4% to 10% of individuals of African descent.
Reduced enzyme clearance
You carry two copies of the T allele defining homozygous CYP2B6*5. Pharmacokinetic studies observe reduced hepatic metabolism and altered clearance rates for substrates such as methadone and bupropion, although overall clinical evidence remains limited. Please share your pharmacogenomic results with a doctor or pharmacist to evaluate any implications for drug dosing.
Uncommon worldwide, occurring in approximately 1% to 2% of people with European ancestry and less than 1% of most other populations.
Understanding the rs28399437 Variant
The rs28399437 variant is a single nucleotide polymorphism (SNP) located within the CYP2B6 gene. In genetic terms, this specific change is a substitution where a cytosine (C) is replaced by a thymine (T) at position 1459 of the gene's coding sequence. This alteration results in a change in the protein structure, specifically replacing the amino acid arginine with cysteine at position 487 (p.Arg487Cys). This variant is a defining feature of the CYP2B6*5 haplotype. Because the CYP2B6 gene is highly polymorphic, meaning it has many different variations, researchers track these specific changes to understand how they might affect the function of the resulting enzyme. By identifying this SNP, scientists can categorize individuals into different groups based on their genetic makeup, which is a foundational step in the field of pharmacogenomics—the study of how genes affect a person's response to drugs.
The Role of the CYP2B6 Gene
The CYP2B6 gene encodes the cytochrome P450 2B6 enzyme. While this enzyme represents a relatively small portion of the total cytochrome P450 content in the liver, it plays a critical role in the metabolism of a wide variety of clinically important substances. These include antiretroviral medications like efavirenz, as well as other drugs used in pain management and cancer treatment. The primary function of the CYP2B6 enzyme is to catalyze the oxidative metabolism of these substrates, essentially helping the body break them down so they can be eliminated. When the gene contains variants like rs28399437, the resulting enzyme may have altered activity levels. This can lead to differences in how quickly or slowly a drug is cleared from the bloodstream, which is why understanding these genetic variations is important for evaluating drug safety and efficacy.
Research and Clinical Evidence
Research into rs28399437 has primarily focused on its impact on drug metabolism. Evidence regarding its clinical significance is currently considered limited. While some studies have investigated its role in the metabolism of specific substrates, results have often been mixed or inconsistent. For example, while some research has explored its association with drug clearance rates, other studies have found no significant differences in clinical outcomes for certain medications when comparing carriers of the variant to non-carriers. Because the CYP2B6 enzyme is influenced by many factors—including other genetic variants, drug-drug interactions, and environmental factors—it is difficult to isolate the effect of this single SNP. Consequently, while it is a recognized marker in pharmacogenomic research, it is not currently used as a standalone predictor for clinical dosing decisions. Always consult with a healthcare provider or pharmacist to discuss how your genetic information may relate to your specific medication regimen.
Population Frequency
The frequency of the rs28399437 variant varies significantly across different ancestral groups. In European populations, the minor allele frequency (MAF) is typically observed between 0.08 and 0.14. In contrast, the variant is less common in African populations, where the MAF is generally reported between 0.02 and 0.05. This inter-ethnic variability is a common feature of many pharmacogenomic markers, highlighting the importance of considering ancestry when interpreting genetic data.
What This Information Means for You
Knowing your genotype for rs28399437 provides insight into your genetic profile, but it does not provide a complete picture of your health or drug response. Because the evidence linking this variant to specific clinical outcomes is limited, it should not be used to make independent medical decisions. Genetic testing results are only one piece of a much larger puzzle that includes your medical history, current medications, and lifestyle. If you have received results regarding this variant, the most appropriate step is to share them with your doctor or a clinical pharmacist. They can interpret these findings within the context of your overall health and determine if any adjustments to your treatment plan are necessary. Never stop or change the dosage of any prescribed medication based on genetic test results without professional medical guidance.
How common is this variant?
The minor allele frequency for rs28399437 is approximately 0.08-0.14 in European populations and 0.02-0.05 in African populations.
Frequently asked questions
Is rs28399437 a diagnostic test for drug response?
No, rs28399437 is not a diagnostic test. It is a genetic marker that researchers study to understand potential variability in drug metabolism, but it is not used on its own to diagnose conditions or predict exact drug responses.
Should I change my medication based on this result?
You should never change your medication or dosage based on genetic test results without consulting your doctor. Genetic markers are only one factor in how your body processes drugs, and your clinician must consider your full medical history.
What does 'limited evidence' mean for this variant?
Limited evidence means that while researchers have identified an association between this variant and certain biological processes, there is not enough consistent clinical data to definitively guide medical treatment or dosing based on this SNP alone.
How can I find out if this variant affects my specific medication?
The best way to understand how this variant might relate to your medications is to speak with your prescribing physician or a clinical pharmacist. They can review your specific drugs and determine if pharmacogenomic testing is relevant to your care.
Sources & further reading
Educational information only, last refreshed 10/28/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Defines the non-functional CYP2B6*18 allele (c.983T>C; p.Ile328Thr) leading to impaired metabolism of efavirenz.
Key variant defining the CYP2B6*6 reduced-function allele influencing efavirenz, methadone, and bupropion clearance.
Missense alteration defining the CYP2B6*18 allele, causing profound enzymatic deficiency and impaired clearance of efavirenz and methadone.
A coding variant that defines the decreased-function CYP2B6*4 allele, influencing plasma concentrations of efavirenz, methadone, and bupropion.
Missense alteration defining the nonfunctional CYP2B6*18 allele common in African populations that slows clearance of efavirenz.
Encodes CYP2B6 c.1459C>T (p.Arg487Cys) defining the CYP2B6*5 allele, associated with reduced clearance of efavirenz and other substrates.