What you carry at this position in your DNA and what research says about it.
Nicotine and Drug Metabolism: 6/10 evidence, 8 publications.
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Sample genotype (not yours): A/A
Typical Nicotine and Medication Clearance Rate
Normal enzyme activity ensures that nicotine and certain medications are cleared from the body at a standard rate. This typical clearance speed means standard dosing guidelines for related drugs are generally appropriate.
What this genotype means: Standard drug clearance; Typical nicotine dependence.
Sample genotype (not yours): A/C
Slower Nicotine and Medication Clearance Rate
A single copy of the variant reduces enzyme levels, leading to slower clearance of nicotine and certain prescription drugs. This can make quitting smoking easier but may increase sensitivity to specific medications.
What this genotype means: Slower nicotine clearance; Increased sensitivity to certain sedatives; Higher risk of efavirenz side effects.
Sample genotype (not yours): C/C
Significantly Slower Nicotine and Medication Clearance Rate
Double copies of the variant significantly decrease enzyme levels, leading to highly prolonged nicotine levels and slower drug clearance. This reduces nicotine dependence but increases the risk of medication-related side effects.
What this genotype means: Highly prolonged nicotine levels; Elevated risk of drug side effects; Decreased osimertinib treatment survival.
Gene function and biological role
Gene Function: The CYP2A6 gene encodes a major liver enzyme belonging to the cytochrome P450 family, which is responsible for metabolizing a wide range of foreign compounds and therapeutic drugs [1]. It is the primary enzyme responsible for the clearance of nicotine, converting it into inactive metabolites [2]. Beyond nicotine, this enzyme plays a crucial role in processing clinically important medications, including certain antivirals, anesthetics, and cancer therapies [1]. Genetic variation in this gene is highly common and serves as the primary driver of differences in how quickly people clear these substances from their bodies [2].
Variant Impact: The rs28399433 variant, commonly known as the CYP2A6*9 allele, is a single nucleotide polymorphism located in the promoter region of the CYP2A6 gene. This specific genetic change disrupts the TATA box, which is a critical regulatory sequence required for gene transcription [3]. As a direct result of this disruption, the gene produces significantly lower levels of messenger RNA, leading to reduced enzyme expression and slower metabolic activity [3]. This reduction in functional enzyme levels alters the clearance rates of nicotine and several prescription medications [2].
Key Insight: Slower nicotine metabolism can actually make it easier to quit smoking because nicotine remains in the bloodstream longer, reducing the frequency of cravings.
Location: CYP2A6. Chromosome 19 · 19q13.2 · 40.9 Mb
Estimated prevalence by population
Global 83.9%; European 87.0%; African 84.5%; East Asian 60.0%; South Asian 74.4%; Americas 81.8%; Ashkenazi 87.2%; Finnish 78.0%; Middle Eastern 90.0%; Amish 95.7%.
Estimated AA genotype frequency.
Global 15.3%; European 12.6%; African 14.9%; East Asian 34.9%; South Asian 23.7%; Americas 17.2%; Ashkenazi 12.4%; Finnish 20.6%; Middle Eastern 9.8%; Amish 4.3%.
Estimated AC genotype frequency.
Global 0.8%; European 0.5%; African 0.7%; East Asian 5.1%; South Asian 1.9%; Americas 0.9%; Ashkenazi 0.4%; Finnish 1.4%; Middle Eastern 0.3%; Amish < 0.1%.
Estimated CC genotype frequency.
Showing effects for A/A genotype
Neurology & Mental Health
Addiction & Reward
Nicotine Dependence. Evidence: 5/10. Source: PMID 22046326. Typical Severity.
Pharmacogenomics
Antimicrobial & Antiviral Response
Efavirenz Metabolism. Evidence: 6/10. Source: PMID 24729586. Typical Clearance.
Anesthesia Response
Dexmedetomidine Sedation. Evidence: 5/10. Source: PMID 35873555. Typical Sedation.
Cancer & Oncology
Lung Cancer
Lung Cancer. Evidence: 3/10. Source: PMID 19339270. Typical Risk.
Cancer Prognosis & Treatment Outcome
Osimertinib Survival. Evidence: 5/10. Source: PMID 38026963. Typical Survival.
Showing effects for A/C genotype
Nicotine Dependence. Evidence: 5/10. Source: PMID 22046326. Reduced Severity.
Efavirenz Metabolism. Evidence: 6/10. Source: PMID 24729586. Slower Clearance.
Dexmedetomidine Sedation. Evidence: 5/10. Source: PMID 35873555. Increased Sedation.
Lung Cancer. Evidence: 3/10. Source: PMID 19339270. Lower Risk.
Showing effects for C/C genotype
Osimertinib Survival. Evidence: 5/10. Source: PMID 38026963. Decreased Survival.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Two copies of the common A allele result in standard expression of the CYP2A6 enzyme in the liver. This normal metabolic capacity means that nicotine is cleared from the bloodstream at a typical rate, which is associated with average smoking patterns and standard nicotine dependence levels in smokers [1]. For individuals undergoing HIV therapy with efavirenz, this genotype is linked to standard drug clearance and a typical risk of concentration-related side effects [2]. Similarly, standard sensitivity is expected during medical procedures involving the sedative dexmedetomidine [3]. Because the enzyme clears tobacco-specific carcinogens at a normal rate, smokers with this genotype exhibit a typical baseline risk for tobacco-related lung cancers compared to slow metabolizers [4]. Overall, standard clinical dosing protocols for CYP2A6-metabolized drugs are typically highly effective for this group.
Standard drug clearance; Typical nicotine dependence.
Sample genotype: AC (Heterozygous)
One copy of the C variant reduces the expression of the CYP2A6 enzyme, resulting in a moderately slower metabolic rate. Because nicotine remains in the bloodstream longer, smokers with this genotype often smoke fewer cigarettes per day and experience milder withdrawal symptoms, making smoking cessation more achievable [1]. However, this slower clearance rate also affects how the body processes several important medications. For example, individuals taking the HIV medication efavirenz may experience higher blood concentrations of the drug, which can increase the risk of neuropsychiatric side effects [2]. Slower metabolism also increases sensitivity to the sedative dexmedetomidine, potentially leading to deeper or more prolonged sedation during medical procedures [3]. Additionally, slower enzyme activity may reduce the metabolic activation of certain tobacco-specific carcinogens, which is linked to a lower risk of developing lung cancer among smokers [4].
Slower nicotine clearance; Increased sensitivity to certain sedatives; Higher risk of efavirenz side effects.
Sample genotype: CC (Homozygous)
Two copies of the C variant lead to a pronounced reduction in CYP2A6 enzyme expression due to the disrupted promoter region. Nicotine is cleared from the body very slowly, which often results in significantly lower nicotine dependence, fewer cigarettes smoked per day, and a higher likelihood of successfully quitting smoking [1]. While this slow metabolism is beneficial for smoking cessation, it presents challenges for several clinical therapies. Patients treated with the HIV drug efavirenz are at a higher risk for elevated drug levels and associated toxicities [2]. During anesthesia, this genotype is associated with heightened sensitivity and prolonged sedation when using dexmedetomidine [3]. Furthermore, in cancer treatments such as osimertinib therapy for non-small cell lung cancer, this slow-metabolizer status has been linked to decreased progression-free survival [4]. Conversely, for active smokers, the reduced activation of tobacco-specific pro-carcinogens translates to a lower risk of tobacco-induced lung cancer [5].
Highly prolonged nicotine levels; Elevated risk of drug side effects; Decreased osimertinib treatment survival.
Variants with shared genetic architecture
rs56113850 · CYP2A6 Gene · Chr 19 · Nicotine Metabolism
rs1801272 · CYP2A6 Gene · Chr 19 · Nicotine Metabolism
rs28399454 · CYP2A6 Gene · Chr 19 · Nicotine Metabolism
CYP2A6 and GABRA2 Gene Polymorphisms are Associated With Dexmedetomidine Drug Response.
'Smoking genes': a genetic association study.
Content updated August 2026.
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