CYP2D6*41 and rs28371725: Understanding Decreased Drug Metabolism
The rs28371725 variant is a key genetic marker that defines the CYP2D6*41 allele, which is associated with decreased enzymatic activity of the CYP2D6 protein. This genetic variation can influence how an individual's body processes certain medications, including specific opioids, antidepressants, and antiarrhythmics.
What each genotype means
Normal enzyme activity
This genotype represents the presence of the reference allele at this position, which is typically associated with normal CYP2D6 enzyme function. Individuals with this result do not carry the specific genetic change that defines the reduced-function CYP2D6*41 allele at this site. Please discuss any medication-related concerns or dosing questions with your clinician or pharmacist.
This is the most common genotype observed in most global populations.
Potential reduced enzyme activity
This genotype indicates you carry one copy of the variant associated with the CYP2D6*41 allele, which is known to cause decreased enzymatic metabolism of certain drugs. Because you also carry a normal copy, your overall ability to process medications like opioids or antidepressants may be intermediate. Please discuss your medication history and potential dosing adjustments with your clinician or pharmacist.
Carried by a significant portion of individuals of European and Middle Eastern ancestry, with a minor allele frequency of approximately 8-10%.
Reduced enzyme activity
This genotype indicates you carry two copies of the variant associated with the CYP2D6*41 allele, which is characterized as a reduced-function allele. Research suggests this may lead to slower metabolism of common drugs, including certain antidepressants and antiarrhythmics, due to an alternative splicing defect. Please consult with your clinician or pharmacist to determine if your current medication regimen requires adjustment.
This genotype is less common than the heterozygous state but is observed in populations with European and Middle Eastern ancestry.
What is the rs28371725 Variant?
The rs28371725 variant is a single nucleotide polymorphism (SNP) located within the CYP2D6 gene. In the context of pharmacogenomics, this specific SNP serves as a defining marker for the CYP2D6*41 allele. The CYP2D6 gene provides instructions for making an enzyme that plays a critical role in the metabolism of approximately 25% of all clinically used drugs. When the rs28371725 variant is present, it contributes to an alternative splicing defect, which ultimately results in the production of a less functional enzyme. Because this variant alters the efficiency of the enzyme, it is categorized as a decreased-function allele. Understanding this variant is important for researchers studying how genetic differences contribute to variability in drug response among different individuals.
The Role of the CYP2D6 Gene
The CYP2D6 gene is part of the cytochrome P450 family, a group of enzymes primarily found in the liver that are responsible for breaking down toxins and drugs. Because CYP2D6 is involved in the metabolism of a wide array of medications—including beta-blockers, antidepressants, and various opioids—the functional status of this gene is highly significant in clinical pharmacology. Individuals with fully functional CYP2D6 enzymes are typically classified as normal metabolizers. However, genetic variations like the *41 allele can lead to reduced enzyme activity. This means that for certain drugs, the body may process the medication more slowly than expected. This can lead to higher concentrations of the drug in the bloodstream, potentially increasing the risk of side effects or, in the case of prodrugs that require activation, reducing the drug's therapeutic effectiveness.
Research and Clinical Evidence
Research into the CYP2D6*41 allele, marked by rs28371725, has established it as a significant factor in pharmacogenomics. Clinical guidelines, such as those provided by the Clinical Pharmacogenetics Implementation Consortium (CPIC), assign the *41 allele a decreased function activity value. Studies have shown that individuals carrying this allele may experience altered responses to medications metabolized by the CYP2D6 pathway. While the evidence is robust enough to be included in clinical genotyping panels, the clinical impact can vary depending on the specific drug and the individual's overall genetic profile, including other co-inherited alleles. It is important to note that while genetic associations are well-documented, they are not absolute predictors of clinical outcomes. Factors such as age, liver function, and concurrent use of other medications also play a major role in how a patient responds to treatment.
Population Frequency
The frequency of the CYP2D6*41 allele varies significantly across different global populations. It is considered a common variant in European and Middle Eastern ancestries, with a minor allele frequency (MAF) typically ranging between 0.08 and 0.10 in European populations. Research has also highlighted its prevalence in various Arab populations, where it has been identified as a major reduced-function allele. In contrast, its frequency can be lower in other ethnic groups, such as East Asian populations, where other variants like *10 are more common. This heterogeneity underscores the importance of considering ancestral background when interpreting pharmacogenetic data. Because the distribution of these alleles is not uniform, the clinical relevance of testing for this specific variant may differ depending on the patient's heritage.
Managing Your Genetic Information
If you have received information about your CYP2D6 genotype, it is essential to understand that this data is only one piece of a larger clinical puzzle. Genetic testing for this variant does not provide a diagnosis, nor does it dictate a specific medical outcome. Instead, it provides information that your healthcare provider can use to make more informed decisions about medication selection and dosing. You should never change or stop taking a prescribed medication based on genetic test results without first consulting your doctor or pharmacist. They are the only ones qualified to interpret these results in the context of your full medical history, current health status, and other medications you may be taking. Always discuss your pharmacogenetic profile with a qualified clinician to ensure your treatment plan is safe and effective for your specific needs.
How common is this variant?
The CYP2D6*41 allele is common in European and Middle Eastern populations, with a minor allele frequency typically between 0.08 and 0.10.
Frequently asked questions
What does it mean to be a CYP2D6 intermediate metabolizer?
An intermediate metabolizer has reduced CYP2D6 enzyme activity, often due to carrying one decreased-function allele like *41. This means the body may process certain drugs more slowly than normal, which might require dosage adjustments.
Does having the CYP2D6*41 allele mean I cannot take certain medications?
Not necessarily. It simply means your body may process those medications differently. Your doctor can use this information to choose the most appropriate drug or adjust the dose to ensure it is safe and effective for you.
Is the rs28371725 variant the same as the CYP2D6*41 allele?
The rs28371725 SNP is a key genetic marker used to define the CYP2D6*41 allele. While they are closely linked in clinical testing, the *41 allele is a specific haplotype defined by this and other associated variants.
Should I get tested for CYP2D6 variants?
Pharmacogenetic testing is typically recommended by healthcare providers when a patient is starting a medication known to be processed by the CYP2D6 enzyme. You should discuss the necessity of such testing with your physician.
Sources & further reading
Educational information only, last refreshed 9/21/2026. 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.
Defines the CYP2D6*29 variant (p.Val338Met) conferring decreased metabolic capacity, primarily observed in populations of African descent.
Promoter variant defining the CYP2D6*41 allele, associated with reduced enzyme expression and decreased metabolic capacity for various drugs.
Defines the non-functional CYP2D6*41 splice defect associated with intermediate metabolizer phenotype affecting codeine, tamoxifen, and SSRI metabolism.