CYP2D6 rs72549303: What Your Genotype Means
The rs72549303 variant is a specific genetic change within the CYP2D6 gene that defines the non-functional *29 star allele. This variant is associated with a decreased capacity to metabolize certain medications and is primarily observed in individuals of African descent.
What each genotype means
Normal enzyme activity
This genotype represents the absence of the specific genetic change associated with the CYP2D6*29 allele. Individuals with this genotype typically possess normal metabolic capacity for medications processed by the CYP2D6 enzyme, though this can be influenced by other genetic factors. Please discuss any medication dosing or concerns with your clinician or pharmacist.
This is the most common genotype in most global populations, though it is less frequent in populations of African descent where the *29 allele is more prevalent.
Reduced enzyme activity
This genotype indicates you carry one copy of the CYP2D6*29 variant, which is associated with decreased metabolic capacity for certain drugs. Because you also carry a normal copy, your ability to process medications may be intermediate compared to those with two normal copies. Please consult your healthcare provider or pharmacist regarding how this may affect your response to specific medications.
This genotype is observed primarily in individuals of African ancestry, reflecting the distribution of the *29 allele in these populations.
Decreased enzyme activity
This genotype indicates you carry two copies of the CYP2D6*29 variant, which is known to result in reduced function of the CYP2D6 enzyme. This may lead to slower processing of certain medications, potentially requiring dosage adjustments to ensure safety and efficacy. Always consult with your clinician or pharmacist before making changes to your medication regimen.
This genotype is rare and found almost exclusively in populations of African descent, consistent with the frequency of the *29 allele.
Understanding the rs72549303 Variant
The rs72549303 variant is a single nucleotide polymorphism (SNP) located within the CYP2D6 gene, which provides instructions for making an enzyme essential for drug metabolism. In the context of pharmacogenomics, this specific SNP is a defining component of the CYP2D6*29 star allele. Star allele nomenclature is a standardized system used by researchers to categorize different versions of the CYP2D6 gene based on their functional impact. When this variant is present, it alters the structure of the resulting enzyme, which can lead to a reduction in its ability to process or break down various chemical compounds, including many commonly prescribed medications. Because the CYP2D6 enzyme is responsible for metabolizing approximately 25% of clinically available drugs, variations like rs72549303 are significant subjects of study in precision medicine.
The Role of the CYP2D6 Gene
The CYP2D6 gene belongs to the cytochrome P450 family, a group of enzymes primarily found in the liver that play a critical role in the metabolism of xenobiotics, including therapeutic drugs. The enzyme acts as a biological catalyst, transforming medications into forms that the body can either utilize or eliminate. Because individuals inherit two copies of the CYP2D6 gene—one from each parent—the combination of these copies determines an individual's overall metabolic phenotype. Phenotypes range from poor metabolizers, who process drugs very slowly, to ultrarapid metabolizers, who process them very quickly. The *29 allele, which includes the rs72549303 variant, is classified as a decreased-function allele. This means that if an individual carries this variant, their liver may not process certain drugs at the expected rate, potentially leading to higher concentrations of the medication in the bloodstream or, conversely, reduced efficacy if the drug requires activation by the enzyme.
Research and Clinical Evidence
Scientific research has established that the *29 allele is associated with diminished metabolic activity for various CYP2D6 substrates, such as certain antidepressants, antipsychotics, and opioids. The evidence for this association is grounded in pharmacokinetic studies that compare drug levels in individuals carrying the *29 allele against those with normal-function alleles. While the association is well-documented in scientific literature, the clinical impact can vary significantly depending on the specific medication being administered and the individual's other genetic factors. It is important to note that pharmacogenomic evidence is complex; the presence of a single variant does not provide a complete picture of how a person will respond to a drug. Consequently, clinical guidelines often emphasize that genetic testing results should be interpreted by healthcare professionals who can integrate this information with other clinical factors, such as age, liver function, and concurrent medication use.
Population Frequency and Distribution
The distribution of the rs72549303 variant is highly ancestry-specific. Research indicates that the *29 allele is found primarily in populations of African descent, with minor allele frequencies typically ranging between 5% and 12%. In contrast, this variant is largely absent in European and East Asian populations. This disparity highlights the importance of diversity in genomic research, as many pharmacogenomic studies have historically focused on European cohorts, potentially leaving gaps in our understanding of drug response in other global populations. Recognizing these frequency differences is essential for equitable healthcare, as it ensures that clinical guidelines and diagnostic tools are relevant and accurate for all patients, regardless of their ancestral background.
Navigating Your Genetic Information
If you have received information about your CYP2D6 status, it is natural to have questions about what it means for your health. However, it is crucial to understand that genetic variants are only one piece of a much larger puzzle. You should never use genetic information to make decisions about starting, stopping, or changing the dosage of any medication without consulting your doctor or pharmacist. A clinician can evaluate your specific genotype in the context of your medical history and current treatment plan. They are the only ones qualified to determine if a dosage adjustment is necessary or if an alternative medication might be more appropriate for you. Genetic testing for pharmacogenomics is a tool to support personalized care, not a substitute for professional medical judgment.
How common is this variant?
The rs72549303 variant has a minor allele frequency of approximately 5-12% in African populations and is essentially absent in European and East Asian populations.
Frequently asked questions
What does it mean to be a CYP2D6 poor metabolizer?
A poor metabolizer has two non-functional copies of the CYP2D6 gene, leading to a significantly reduced ability to process certain drugs. This can result in higher drug levels in the body, increasing the risk of side effects.
Should I get tested for CYP2D6 variants?
Pharmacogenomic testing is generally recommended only when a patient is prescribed a medication known to be processed by the CYP2D6 enzyme. You should discuss the necessity of such testing with your healthcare provider.
Does having the *29 allele mean I cannot take certain medications?
Not necessarily. Having the *29 allele may mean your doctor needs to adjust your dosage or choose a different medication to ensure safety and effectiveness. Always consult your clinician before making changes to your prescriptions.
Are there other genes that affect drug metabolism?
Yes, many genes in the cytochrome P450 family, such as CYP2C19 and CYP2C9, play significant roles in how the body processes various medications. Pharmacogenomics is a broad field that considers the interaction of many different genetic factors.
Sources & further reading
Educational information only, last refreshed 9/29/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in CYP2D6
This variant is a key marker for the CYP2D6*10 allele, which results in reduced enzymatic activity and altered metabolism of various psychiatric and analgesic medications.
This variant defines the CYP2D6*4 non-functional allele, which causes impaired metabolism of numerous clinically prescribed medications including antidepressants, tamoxifen, and codeine.
Defines the CYP2D6*17 allele (p.Thr107Ile), which exhibits reduced enzyme activity towards substrates like codeine and certain antidepressants.
Promoter variant defining the CYP2D6*41 allele, associated with reduced enzyme expression and decreased metabolic capacity for various drugs.
Defines the CYP2D6*6 deletion variant (1707delT) leading to a premature stop codon and loss of enzyme function.
Defines the non-functional CYP2D6*41 splice defect associated with intermediate metabolizer phenotype affecting codeine, tamoxifen, and SSRI metabolism.