What you carry at this position in your DNA and what research says about it.
Drug Metabolism and Heart Risk: 8/10 evidence, 35 publications.
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Sample genotype (not yours): C/C
Typical Drug Metabolism and Baseline Heart Risk
Typical enzyme activity ensures standard processing of many common medications. Baseline susceptibility to cardiovascular conditions is maintained.
What this genotype means: Standard processing of common medications; Baseline risk for coronary heart disease.
Sample genotype (not yours): C/T
Altered Drug Clearance and Elevated Heart Risk
Faster clearance of some medications may reduce their effectiveness, while slower clearance of others increases sensitivity. An elevated risk of coronary heart disease is also associated with this genotype.
What this genotype means: Altered response to specific medications; Increased risk of coronary heart disease.
Sample genotype (not yours): T/T
Significantly Altered Drug Response and Higher Heart Risk
Slower metabolism of pain medications increases the risk of side effects, while faster clearance of immunosuppressants may reduce efficacy. A significantly higher risk of coronary heart disease is also linked to this genotype.
What this genotype means: Altered response to specific medications; Significantly increased risk of coronary heart disease.
Gene function and biological role
Gene Function: Cytochrome P450 3A4, encoded by the CYP3A4 gene, is one of the most important drug-metabolizing enzymes in the human body [1]. It is primarily expressed in the liver and intestines, where it processes more than half of all clinically prescribed medications [2]. These include common therapeutics such as immunosuppressants, statins, and opioid pain relievers [3]. Variations in this gene can significantly alter how quickly these substances are cleared from the system [4]. Consequently, genetic differences in CYP3A4 can lead to unexpected drug toxicities or treatment failures [5].
Variant Impact: The rs2242480 variant is an intronic single nucleotide polymorphism located in the CYP3A4 gene [2]. This genetic change, historically referred to as the CYP3A4*1G or CYP3A4*36 allele, alters the expression and baseline activity of the CYP3A4 enzyme [1]. It is highly prevalent in East Asian populations, where it frequently co-inherits with other cytochrome P450 variants [6]. Because it modifies enzyme levels, this variant directly impacts the pharmacokinetics of various medications [4]. It has also been linked to differences in susceptibility to certain cardiovascular conditions [7].
Key Insight: This variant acts like a double-edged sword for medications, speeding up the clearance of some drugs while slowing down others, and it is also linked to cardiovascular health.
Location: CYP3A4. Chromosome 7 · 7q22.1 · 99.8 Mb
Estimated prevalence by population
Global 55.1%; European 82.1%; African 7.1%; East Asian 53.8%; South Asian 42.8%; Americas 41.1%; Ashkenazi 79.7%; Finnish 85.1%; Middle Eastern 63.1%; Amish 86.2%.
Estimated CC genotype frequency.
Global 27.7%; European 17.0%; African 39.2%; East Asian 39.1%; South Asian 45.2%; Americas 46.0%; Ashkenazi 19.2%; Finnish 14.3%; Middle Eastern 32.7%; Amish 13.2%.
Estimated CT genotype frequency.
Global 17.2%; European 0.9%; African 53.7%; East Asian 7.1%; South Asian 11.9%; Americas 12.9%; Ashkenazi 1.2%; Finnish 0.6%; Middle Eastern 4.2%; Amish 0.5%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Pharmacogenomics
Immunosuppressant & Biologic Response
Tacrolimus Clearance. Evidence: 8/10. Source: PMID 23459029. Typical Clearance.
Pain Medication Response
Fentanyl Sensitivity. Evidence: 8/10. Source: PMID 21535061. Typical Sensitivity.
Methadone Side Effects. Evidence: 5/10. Source: PMID 21902501. Typical Severity.
Cardiovascular & Metabolic
Heart Disease
Heart Disease. Evidence: 3/10. Source: PMID 21199372. Typical Risk.
Showing effects for C/T genotype
Tacrolimus Clearance. Evidence: 8/10. Source: PMID 23459029. Faster Clearance.
Fentanyl Sensitivity. Evidence: 8/10. Source: PMID 21535061. Higher Sensitivity.
Methadone Side Effects. Evidence: 5/10. Source: PMID 21902501. Increased Severity.
Heart Disease. Evidence: 3/10. Source: PMID 21199372. Elevated Risk.
Showing effects for T/T genotype
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Standard enzyme levels allow for the expected clearance of medications like tacrolimus and fentanyl [1] [2]. Standard dosing guidelines typically apply without genetic adjustments [3]. Baseline susceptibility to coronary heart disease is maintained, showing no elevated genetic risk from this specific locus [4]. Standard responses to pain management therapies are generally observed [5]. No increased risk of severe side effects or withdrawal during methadone therapy is associated with this genotype [6].
Standard processing of common medications; Baseline risk for coronary heart disease.
Sample genotype: CT (Heterozygous)
Accelerated clearance of the immunosuppressant tacrolimus may lead to lower blood concentrations of the drug [1]. Conversely, slower metabolism of fentanyl can increase sensitivity, meaning lower doses may be sufficient for pain control [2] [3]. An increased risk of coronary heart disease has been observed in carriers of this variant allele [4]. Higher susceptibility to severe side effects and withdrawal symptoms during methadone maintenance therapy is also reported [5]. Close clinical monitoring is often helpful when initiating therapies metabolized by this pathway [6].
Altered response to specific medications; Increased risk of coronary heart disease.
Sample genotype: TT (Homozygous)
Slower metabolism of fentanyl and related opioids can lead to higher drug concentrations and a greater risk of adverse effects like reduced breathing [1] [2]. Conversely, rapid clearance of tacrolimus often necessitates higher initial doses to maintain therapeutic levels [3]. A significantly elevated risk of coronary heart disease, with odds ratios up to nearly four-fold, has been documented [4]. Increased severity of side effects and withdrawal symptoms during methadone therapy is also a known risk [5]. These metabolic differences highlight the utility of genotype-guided dosing for specific medications [6].
Altered response to specific medications; Significantly increased risk of coronary heart disease.
Variants with shared genetic architecture
rs35599367 · CYP3A4 Gene · Chr 7 · Medication Clearance Rate
rs2740574 · CYP3A4 Gene · Chr 7 · Prostate Cancer Risk
rs4646437 · CYP3A4 Gene · Chr 7 · Drug Metabolism and Health
Content updated August 2026.
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