BACKGROUND: Caffeine is the most widely consumed stimulant in the world, and individual differences in response to its stimulating effects may explain some of the variability in caffeine consumption within a population. OBJECTIVE: We examined whether genetic variability in caffeine metabolism cytochrome P450 1A2 (CYP1A2) -163A-->C or the main target of caffeine action in the nervous system adenosine A(2A) receptor (ADORA2A) 1083C-->T is associated with habitual caffeine consumption. DESIGN: Subjects (n=2735) were participants from a study of gene-diet interactions and risk of myocardial infarction who did not have a history of hypertension. Genotype frequencies were examined among persons who were categorized according to their self-reported daily caffeine intake, as assessed with a validated food-frequency questionnaire. RESULTS: The ADORA2A, but not the CYP1A2, genotype was associated with different amounts of caffeine intake. Compared with persons consuming 200-400, and >400 mg caffeine/d, respectively. The association was more pronounced among current smokers than among nonsmokers (P for interaction = 0.07). Persons with the ADORA2A TT genotype also were significantly more likely to consume less caffeine (ie, <100 mg/d) than were carriers of the C allele P=0.011 (nonsmokers), P=0.008 (smokers). CONCLUSION: Our findings show that the probability of having the ADORA2A 1083TT genotype decreases as habitual caffeine consumption increases. This observation provides a biologic basis for caffeine consumption behavior and suggests that persons with this genotype may be less vulnerable to caffeine dependence.
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