CYP3A4 rs28365046: What Your Genotype Means
The rs28365046 variant is a genetic change located within the CYP3A4 gene, which plays a critical role in how the body processes medications. Research has linked this specific variant to an increased risk of liver toxicity in patients undergoing treatment for tuberculosis.
What each genotype means
Typical enzyme activity
This genotype represents the most common form of the CYP3A4 gene, often referred to as the *1/*1 wild-type. Research suggests individuals with this profile typically exhibit standard metabolic activity for drugs processed by the CYP3A4 enzyme. Please discuss any medication dosing or concerns regarding drug-induced liver injury with your clinician or pharmacist.
This is the most common genotype observed across all global populations.
Altered metabolic risk
This genotype, which includes one copy of the *18 variant (often denoted as *1/*18), has been associated in some studies with an increased risk of drug-induced hepatotoxicity, particularly in the context of anti-tuberculosis treatment. The clinical significance of this variant is considered limited and may be influenced by other factors such as pre-existing liver health. Please consult your healthcare provider or pharmacist regarding your specific medication management.
This genotype is more frequently observed in East Asian populations compared to other ancestral groups.
Increased metabolic risk
This genotype represents two copies of the *18 variant (*18/*18). Research indicates that individuals with this profile may have altered metabolism of certain medications, such as tacrolimus, and potentially a higher susceptibility to drug-induced liver injury. Because evidence is limited, you should discuss the implications of this genotype for your specific treatment plan with your clinician or pharmacist.
This genotype is rare, though it is more commonly identified in East Asian populations than in other groups.
Understanding the rs28365046 Variant
The rs28365046 variant is a specific single nucleotide polymorphism (SNP) found within the CYP3A4 gene. In the scientific literature, this variant is frequently referred to as the CYP3A4*18 allele. SNPs are the most common type of genetic variation among people, representing a difference in a single building block of DNA. Because this variant is located in a gene responsible for drug metabolism, researchers study it to understand why individuals may respond differently to the same medical treatments. While genetic variations are a normal part of human diversity, some can alter the efficiency of enzymes that break down drugs, potentially leading to higher or lower levels of medication in the bloodstream. Identifying these variants is a key focus of pharmacogenomics, the field that explores how your unique genetic makeup influences your response to drugs.
The Role of the CYP3A4 Gene
The CYP3A4 gene provides instructions for making an enzyme called cytochrome P450 3A4. This enzyme is primarily produced in the liver and is responsible for the metabolism of a vast array of substances, including approximately 50% of all clinically used drugs. By breaking down these compounds, the CYP3A4 enzyme helps the body clear medications and other toxins from the system. Because it is involved in processing so many different drugs, variations in the CYP3A4 gene can have significant clinical implications. When the enzyme's function is altered by a genetic variant, it may lead to either the rapid breakdown of a drug, rendering it ineffective, or the slow breakdown of a drug, which can cause it to accumulate to toxic levels. Understanding the function of this gene is essential for predicting how a patient might react to various therapeutic agents.
Research and Clinical Associations
Current research has investigated the link between the CYP3A4*18 variant (rs28365046) and anti-tuberculosis drug-induced hepatotoxicity (ATDH). Hepatotoxicity refers to liver damage caused by exposure to drugs or other substances. Studies have observed that individuals carrying this variant may have a higher risk of experiencing liver injury when treated with standard anti-tuberculosis medications. Specifically, some data suggest that heterozygous carriers—those who have one copy of the variant—show a statistically significant increase in the risk of developing liver toxicity compared to those without the variant. It is important to note that the evidence for this association is currently considered limited, and the effect may be modulated by other factors, such as pre-existing liver disease. Because this is an area of ongoing research, these findings should be viewed as a starting point for clinical discussion rather than a definitive diagnostic tool.
Population Frequency
Genetic variants are not distributed equally across all human populations. The CYP3A4*18 variant is notably more common in East Asian populations compared to other ancestral groups. This variation in frequency is a common theme in pharmacogenomics, where certain alleles that influence drug metabolism are enriched in specific geographic or ethnic groups. Understanding these population-specific frequencies is vital for researchers and clinicians, as it helps in tailoring medical guidelines to the populations most likely to be affected. While the variant is more prevalent in East Asian cohorts, it remains important to consider individual genetic testing when assessing personal risk, as population-level data cannot predict an individual's specific response to a medication.
What This Information Means for You
If you are aware that you carry the rs28365046 variant, it is important to understand that this information is for educational purposes and does not constitute a medical diagnosis. Genetic markers are only one piece of a complex puzzle that includes your overall health, other medications you may be taking, and your medical history. You should never make changes to your prescribed medications based on genetic information without first consulting your healthcare provider or a pharmacist. These professionals are equipped to interpret your genetic results in the context of your specific clinical situation. They can help determine if alternative dosing or different medications are appropriate for you. Always prioritize professional medical advice when making decisions about your treatment plan, especially when dealing with conditions that require long-term medication like tuberculosis.
How common is this variant?
The CYP3A4*18 variant is found at higher frequencies in East Asian populations compared to other global ancestral groups.
Frequently asked questions
Is the rs28365046 variant a cause of liver disease?
No, the variant itself is not a disease. It is a genetic marker that may influence how your liver processes certain medications, which can potentially increase the risk of drug-induced liver injury.
Should I get tested for this variant before starting medication?
Routine genetic testing for this specific variant is not standard practice for everyone. You should discuss the necessity of pharmacogenetic testing with your doctor if you are concerned about your response to specific medications.
Does having the variant mean I will definitely have liver problems?
No, having the variant does not guarantee that you will experience liver toxicity. It is a risk factor, and many other variables, such as diet, alcohol consumption, and other medications, play a significant role in liver health.
Can I change my diet to compensate for this variant?
There is no evidence that diet can negate the effects of this genetic variant on drug metabolism. Always follow the guidance of your healthcare provider regarding your treatment plan and any necessary lifestyle adjustments.
Sources & further reading
Educational information only, last refreshed 9/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs28365046?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in CYP3A4
This variant is highly prevalent in populations of African and indigenous descent and is linked to increased rivaroxaban exposure and potential bleeding risk.
Intronic CYP3A4 variant (CYP3A4*1G) associated with altered enzyme expression and clinical response to various medications including tacrolimus and statins.
CYP3A4 regulatory variant influencing transcription levels and downstream drug metabolism for various antineoplastics and immunosuppressants.
This SNP is associated with the activity of the major drug-metabolizing enzyme CYP3A4.
This variant defines the CYP3A4*20 allele, which is associated with a loss of function in the metabolism of various clinically important drugs.
The defining SNP for the CYP3A4*22 allele, which leads to significantly reduced metabolism of statins and immunosuppressants.