What you carry at this position in your DNA and what research says about it.
Caffeine and Drug Metabolism: 5/10 evidence, 14 publications.
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Sample genotype (not yours): G/G
Typical Caffeine and Drug Metabolism
This genotype is associated with normal CYP1A2 enzyme activity. You likely process caffeine, theophylline, and clopidogrel at a standard rate.
What this genotype means: Standard clearance of caffeine; Typical response to clopidogrel; Baseline lung cancer risk.
Sample genotype (not yours): A/A
Slowest Caffeine and Drug Metabolism
Carrying two copies of the A allele significantly reduces CYP1A2 enzyme activity. This leads to the slowest clearance of caffeine and several medications.
What this genotype means: Slowest clearance of caffeine; Highest bleeding risk on clopidogrel; Elevated lung cancer risk in non-Asians.
Sample genotype (not yours): G/A
Slower Caffeine and Drug Metabolism
Carrying one copy of the A allele is linked to reduced CYP1A2 enzyme activity. This can lead to slower clearance of caffeine and certain medications.
What this genotype means: Slower clearance of caffeine; Increased bleeding risk on clopidogrel; Slightly elevated lung cancer risk in non-Asians.
Gene function and biological role
Gene Function: The CYP1A2 gene encodes cytochrome P450 1A2, a major liver enzyme responsible for metabolizing a wide range of foreign compounds. This enzyme plays a critical role in clearing dietary substances like caffeine, environmental toxins, and several prescription medications from the body [1]. It is also involved in activating certain pre-carcinogenic compounds into active cancer-causing agents [2]. Genetic variations in this gene can significantly alter enzyme activity, leading to wide differences in how individuals process medications and environmental chemicals [1].
Variant Impact: The rs2069514 variant, also known as -3860G>A, is located in the promoter region of the CYP1A2 gene and defines the CYP1A2*1C allele. This genetic change is associated with decreased transcriptional activity and lower inducibility of the CYP1A2 enzyme, particularly in response to environmental factors like cigarette smoke [1]. Slower enzyme expression leads to reduced clearance of drugs and substances metabolized by this pathway [3]. Consequently, individuals carrying the A allele may experience prolonged drug effects, higher risks of side effects, and altered susceptibility to certain cancers [2].
Key Insight: Carrying the A allele reduces the liver's ability to clear caffeine, meaning the stimulating effects of a single cup of coffee can last significantly longer in your system.
Location: CYP1A2. Chromosome 15 · 15q24.1 · 74.7 Mb
Estimated prevalence by population
Global 77.7%; European 97.4%; African 52.2%; East Asian 54.1%; South Asian 84.2%; Americas 53.0%; Ashkenazi 93.4%; Finnish 90.4%; Middle Eastern 90.1%; Amish 74.6%.
Estimated GG genotype frequency.
Global 19.1%; European 2.6%; African 40.1%; East Asian 38.9%; South Asian 15.1%; Americas 39.6%; Ashkenazi 6.5%; Finnish 9.3%; Middle Eastern 9.7%; Amish 23.5%.
Estimated GA genotype frequency.
Global 3.2%; European < 0.1%; African 7.7%; East Asian 7.0%; South Asian 0.7%; Americas 7.4%; Ashkenazi 0.1%; Finnish 0.2%; Middle Eastern 0.3%; Amish 1.9%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Nutrition & Metabolism
Caffeine & Stimulant Metabolism
Caffeine Metabolism. Evidence: 5/10. Source: PMID 10101295. Typical.
Pharmacogenomics
Anticoagulant & Blood Thinner Response
Clopidogrel Response. Evidence: 5/10. Source: PMID 24762860. Typical Risk.
Cancer & Oncology
Lung Cancer
Lung Cancer. Evidence: 3/10. Source: PMID 26015935. Typical Risk.
Organ Systems
Respiratory Health
Theophylline Metabolism. Evidence: 5/10. Source: PMID 12732846. Typical.
Neurology & Mental Health
Addiction & Reward
Opioid Addiction Risk. Evidence: 5/10. Source: PMID 36744646. Typical Risk.
Showing effects for A/A genotype
Caffeine Metabolism. Evidence: 5/10. Source: PMID 10101295. Slowest.
Clopidogrel Response. Evidence: 5/10. Source: PMID 24762860. Increased Risk.
Lung Cancer. Evidence: 3/10. Source: PMID 26015935. Increased Risk.
Theophylline Metabolism. Evidence: 5/10. Source: PMID 12732846. Slowest.
Opioid Addiction Risk. Evidence: 5/10. Source: PMID 36744646. Decreased Risk.
Showing effects for G/A genotype
Caffeine Metabolism. Evidence: 5/10. Source: PMID 10101295. Slower.
Theophylline Metabolism. Evidence: 5/10. Source: PMID 12732846. Slower.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Possessing two copies of the functional, ancestral G allele results in normal baseline levels of the CYP1A2 enzyme [1]. This standard enzyme activity ensures that caffeine is cleared from the body at a typical rate, preventing the prolonged jitteriness or sleep disruption often experienced by slow metabolizers [1]. When treated with the blood thinner clopidogrel, this genotype is associated with a standard response and a typical risk profile for bleeding or adverse events [2]. Slower-cleared medications like theophylline are also processed normally, reducing the likelihood of unexpected drug accumulation [3]. Furthermore, meta-analyses suggest that having the G/G genotype is associated with a typical baseline risk for lung cancer compared to those carrying the A variant [4]. Overall, this genotype represents the standard metabolic profile for CYP1A2 substrates.
Standard clearance of caffeine; Typical response to clopidogrel; Baseline lung cancer risk.
Sample genotype: AA (Homozygous)
Being homozygous for the CYP1A2*1C allele results in a marked decrease in CYP1A2 enzyme activity [1]. This genetic profile leads to significantly slower metabolism of caffeine, meaning even small amounts can have long-lasting effects on sleep and heart rate [1]. When taking the antiplatelet drug clopidogrel, this genotype is associated with a higher risk of bleeding complications and adverse outcomes [2]. Slower clearance is also documented for the respiratory drug theophylline and the antipsychotic quetiapine, which can increase the risk of drug-related side effects [3] [4]. Furthermore, meta-analyses indicate that non-Asian individuals with the A/A genotype have an elevated susceptibility to lung cancer [5]. Conversely, this genotype has been associated with a decreased risk of developing opioid use disorder [6].
Slowest clearance of caffeine; Highest bleeding risk on clopidogrel; Elevated lung cancer risk in non-Asians.
Sample genotype: GA (Heterozygous)
Carrying one copy of the CYP1A2*1C allele reduces the overall production and inducibility of the CYP1A2 enzyme [1]. This reduction is particularly notable in smokers, who typically experience less enzyme induction than G/G individuals [1]. As a result, caffeine remains in the system longer, which can prolong its stimulating effects and increase sensitivity to caffeine-induced jitters [1]. When treated with the antiplatelet drug clopidogrel, carriers of this variant have been shown to have an increased risk of bleeding and overall mortality [2]. Slower metabolism is also observed for other drugs like theophylline, potentially requiring careful monitoring of side effects [3]. Additionally, some meta-analyses have linked the A allele to an increased risk of lung cancer in non-Asian populations [4]. Conversely, this genotype has been associated with a decreased risk of developing opioid use disorder [5].
Slower clearance of caffeine; Increased bleeding risk on clopidogrel; Slightly elevated lung cancer risk in non-Asians.
Variants with shared genetic architecture
rs762551 · CYP1A2 Gene · Chr 15 · Caffeine Metabolism
rs2470890 · CYP1A2 Gene · Chr 15 · Caffeine and Drug Response
rs2472304 · CYP1A2 Gene · Chr 15 · Caffeine and Parkinson's
CYP1A2 rs2069514 polymorphism and lung cancer susceptibility: a meta-analysis.
Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma.
Genetic Variants Associated With Opioid Use Disorder.
Content updated August 2026.
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