CYP2C19 rs28365045: Understanding Clopidogrel Response
The rs28365045 variant is a genetic change located within the CYP2C19 gene, which is responsible for producing an enzyme that processes certain medications. This variant is associated with reduced enzyme function, which can influence how effectively an individual metabolizes the antiplatelet drug clopidogrel.
What each genotype means
Normal enzyme activity
This genotype is considered the normal or wild-type state for this position in the CYP2C19 gene. Individuals with this profile typically possess standard enzyme function for metabolizing medications like clopidogrel. Please discuss your medication options and any concerns regarding drug efficacy with your clinician or pharmacist.
This is the most common genotype observed across most global populations.
Reduced enzyme activity
This genotype indicates you carry one copy of a loss-of-function variant, often referred to in literature as part of the *2 or *3 allele groups. This may result in reduced ability to convert clopidogrel into its active form, potentially impacting its antiplatelet effect. Please consult your healthcare provider or pharmacist to discuss whether this genotype is relevant to your current or future medication therapy.
Carried by a significant portion of the population, with higher frequencies often observed in East Asian ancestries compared to Western populations.
Significantly reduced enzyme activity
This genotype indicates you carry two copies of a loss-of-function variant, which is associated with a decreased ability to process certain medications like clopidogrel. Research suggests this may lead to lower levels of the active drug in your system and a potentially higher risk of adverse cardiovascular events when using this specific medication. Please discuss these findings and potential alternative therapies with your clinician or pharmacist.
This genotype is rare in many populations, though it occurs more frequently in certain East Asian groups.
What is the rs28365045 Variant?
The rs28365045 variant is a specific single nucleotide polymorphism (SNP) found within the CYP2C19 gene. In the context of pharmacogenomics, this variant is studied because it sits in a region of the genome that influences the activity of the cytochrome P450 2C19 enzyme. This enzyme is a critical component of the liver's metabolic machinery, responsible for breaking down or activating a wide range of drugs. When a variant like rs28365045 is present, it may alter the structure or expression of this enzyme, potentially leading to differences in how a person's body processes medications. Researchers track these variants to understand why individuals may experience different clinical outcomes when taking the same standard dose of a prescribed medication.
The Role of the CYP2C19 Gene
The CYP2C19 gene provides instructions for making an enzyme that is essential for the metabolism of many common drugs, including clopidogrel. Clopidogrel is a prodrug, meaning it must be converted by the CYP2C19 enzyme into its active form to effectively inhibit platelet aggregation and prevent blood clots. If the CYP2C19 enzyme is not functioning at full capacity due to genetic variations, the conversion of clopidogrel into its active form is often diminished. This can result in lower levels of the active drug in the bloodstream, which may reduce the medication's ability to prevent cardiovascular events like heart attacks or strokes. Understanding the function of this gene is a cornerstone of modern pharmacogenomics, as it helps clinicians identify patients who might require alternative therapies.
Research and Clinical Associations
Scientific research has established a clear link between loss-of-function variants in the CYP2C19 gene and reduced clopidogrel efficacy. Studies have consistently shown that individuals carrying these variants are at a higher risk for adverse cardiovascular events when treated with clopidogrel compared to those with normal enzyme activity. The evidence strength for these associations is considered moderate to strong in clinical literature, leading to formal warnings in drug labeling. However, it is important to note that genetic status is only one factor in drug response; other variables, such as age, diet, and concurrent medications, also play significant roles. Because of these complexities, clinical guidelines often recommend that healthcare providers use genetic testing results to guide the selection of antiplatelet therapy rather than relying on a one-size-fits-all approach.
Navigating Your Genetic Information
If you have received information about your CYP2C19 genotype, it is essential to discuss these results with your physician or a qualified pharmacist. This information should never be used to self-diagnose or to alter your medication regimen without professional medical supervision. A clinician can interpret your specific genotype in the context of your overall health history and current treatment plan. They are the only ones who can determine if a change in medication or dosage is appropriate for your specific needs. While genetic testing provides valuable insights into how your body might process certain drugs, it is just one piece of a larger clinical puzzle. Always consult with your healthcare team before making any decisions regarding your prescribed treatments.
How common is this variant?
The frequency of specific CYP2C19 loss-of-function variants varies significantly across different global populations, with some alleles being more common in East Asian populations compared to others. The rs28365045 variant itself is generally considered rare in many broad population databases.
Frequently asked questions
Does having this variant mean clopidogrel will not work for me?
Not necessarily. While this variant is associated with reduced enzyme activity, it does not mean the drug will have zero effect. Your doctor will consider your genetic results alongside other clinical factors to determine the best treatment strategy.
Should I get tested for CYP2C19 variants?
Genetic testing for CYP2C19 is typically ordered by a cardiologist or primary care physician when they are considering prescribing clopidogrel. You should discuss the necessity and potential benefits of this testing with your healthcare provider.
Can I change my genotype through diet or lifestyle?
No, your genotype is determined at birth and cannot be changed by diet, exercise, or lifestyle modifications. However, your doctor can adjust your medical treatment plan based on your genetic profile.
Are there alternatives to clopidogrel if I have this variant?
Yes, there are alternative antiplatelet medications available that do not rely on the CYP2C19 enzyme for activation. Your physician can evaluate whether an alternative medication is safer and more effective for your specific situation.
Sources & further reading
Educational information only, last refreshed 10/7/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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The CYP2C19*2 loss-of-function splicing defect results in impaired biotransformation of prodrugs including clopidogrel and altered clearance of proton pump inhibitors and select antidepressants.
Defines the CYP2C19*17 increased function allele, conferring rapid or ultrarapid metabolism for CPIC-actionable drugs including clopidogrel, PPIs, and SSRIs.
Variant in the CYP2C19 locus associated with altered metabolism of clopidogrel and proton-pump inhibitors.
Defines the CYP2C19*8 loss-of-function variant (c.358T>C, p.Trp120Arg) which results in no enzymatic activity and impaired metabolism of CYP2C19 substrates.
Defines the non-functional CYP2C19*3 null allele resulting from a premature stop codon, leading to poor metabolism of drugs such as clopidogrel, escitalopram, and proton pump inhibitors.
Defines the CYP2C19*4 allele caused by an ATG start codon alteration that abolishes translation, resulting in reduced or absent drug metabolism capacity.