CYP3A4 rs35599367: What Your Genotype Means
The rs35599367 variant is a genetic change located within the CYP3A4 gene, which is responsible for producing a critical liver enzyme. This specific variant is associated with reduced enzyme activity, which can influence how the body processes certain medications, including statins and immunosuppressants.
What each genotype means
Normal enzyme activity
This genotype is considered the wild-type or reference profile, often referred to as *1/*1 in clinical literature. Individuals with this profile typically exhibit standard CYP3A4 enzyme function for metabolizing medications. Please discuss any medication dosing or potential drug interactions with your clinician or pharmacist.
This is the most common genotype across all global populations.
Reduced enzyme activity
This genotype, often referred to as *1/*22, is associated with reduced CYP3A4 mRNA and protein expression. Research suggests this may lead to altered metabolism of certain medications, such as statins or immunosuppressants, compared to those with the CC genotype. Please consult your healthcare provider or pharmacist regarding how this may influence your specific medication requirements.
Carried by approximately 5-8% of individuals of European ancestry, with varying frequencies in other populations.
Significantly reduced enzyme activity
This genotype, often referred to as *22/*22, is associated with the lowest levels of CYP3A4 enzyme expression among the common variants. This may result in a decreased ability to metabolize specific drugs, potentially requiring dosage adjustments to avoid side effects or ensure therapeutic efficacy. Always discuss your genetic profile and medication management with your clinician or pharmacist.
This genotype is rare in most populations, occurring at a much lower frequency than the heterozygous CT profile.
Understanding the rs35599367 Variant
The rs35599367 variant is a single nucleotide polymorphism (SNP) located in the sixth intron of the CYP3A4 gene. In genetics, an intron is a non-coding region of DNA that sits between the coding segments, or exons, of a gene. While introns do not directly provide the instructions for building a protein, they play a vital role in regulating how genes are expressed. Research has shown that this specific SNP, often referred to as the CYP3A4*22 allele, alters the way the gene's messenger RNA is spliced. This process leads to the production of a non-functional version of the enzyme, ultimately resulting in lower levels of the active CYP3A4 protein in the liver. Because this variant affects the fundamental machinery of gene expression, it is considered a functional genetic marker.
The Role of the CYP3A4 Gene
The CYP3A4 gene provides instructions for making an enzyme that belongs to the cytochrome P450 family. This enzyme is primarily found in the liver and is responsible for the oxidative metabolism of a vast array of substances, including 30% to 50% of all clinically used drugs. By breaking down these compounds, the CYP3A4 enzyme helps the body clear medications and toxins from the system. Because it is involved in the metabolism of so many different drugs, variations in the CYP3A4 gene can have significant implications for how individuals respond to treatment. When the enzyme is less active, drugs may remain in the bloodstream for longer periods or at higher concentrations than intended, which can change the effectiveness or safety profile of a prescribed medication.
Research and Clinical Associations
Scientific research has consistently linked the rs35599367 T-allele to reduced CYP3A4 enzyme activity. Clinical studies have observed that individuals carrying this variant may experience a stronger lipid-lowering response when taking statins, such as simvastatin, because the drug is not broken down as quickly. Similarly, the variant has been studied in the context of immunosuppressant therapy, where reduced metabolism can lead to different drug exposure levels. While the evidence for these associations is considered moderate, it is important to note that drug response is complex and influenced by many factors, including age, diet, other medications, and overall health. The impact of this variant is not universal, and researchers continue to investigate how it interacts with various drug classes in different clinical settings.
Interpreting Your Genetic Information
If you are aware of your genotype for rs35599367, it is important to understand that this information is only one piece of a much larger puzzle regarding your health. Genetic testing results should never be used to make independent decisions about your medications or health care. Because the CYP3A4 enzyme is involved in the metabolism of many different drugs, having a specific genotype does not automatically mean you will experience a specific clinical outcome. If you have questions about how your genetic profile might influence your response to a particular medication, you should discuss this with your physician or a clinical pharmacist. They can interpret your results in the context of your full medical history and current treatment plan to ensure your care is safe and effective.
How common is this variant?
The rs35599367 variant is found in approximately 5-8% of European populations, with frequencies varying across other global ancestries.
Frequently asked questions
What does it mean to be a carrier of the CYP3A4*22 allele?
Being a carrier means you have inherited at least one copy of the rs35599367 T-allele. This variant is associated with reduced activity of the CYP3A4 enzyme, which may affect how your body processes certain medications.
Does this variant mean I cannot take certain medications?
No, it does not mean you cannot take certain medications. It simply means your body may metabolize them differently, which your doctor can account for when determining the appropriate dosage for you.
Is the rs35599367 variant the same as CYP3A4*22?
Yes, rs35599367 is the specific SNP identifier used to define the CYP3A4*22 allele. They refer to the same genetic variation.
Should I get tested for this variant before starting a new medication?
Routine testing for this variant is not standard for everyone. You should discuss the necessity of pharmacogenetic testing with your healthcare provider based on the specific medication you are being prescribed.
Sources & further reading
Educational information only, last refreshed 10/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant is highly prevalent in populations of African and indigenous descent and is linked to increased rivaroxaban exposure and potential bleeding risk.
The CYP3A4*18 variant is significantly associated with the risk of anti-tuberculosis drug-induced hepatotoxicity, with effects modulated by pre-existing liver disease status.
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.