Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption.
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.


METHODS
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 <100 mg caffeine/d, the odds ratios for having the ADORA2A TT genotype were 0.74 (95% CI: 0.53, 1.03), 0.63 (95% CI: 0.48, 0.83), and 0.57 (95% CI: 0.42, 0.77) for those consuming 100-200, >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)].


CONCLUSIONS
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.
Cornelis
Marilyn C
MC
Department of Nutritional Sciences, University of Toronto, Canada.
El-Sohemy
Ahmed
A
Campos
Hannia
H
D000428:Alcohol Drinking; D002110:Caffeine / Q000008:administration & dosage*; D016022:Case-Control Studies; D003364:Costa Rica; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004327:Drinking Behavior / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D043683:Receptors, Adenosine A2 / Q000235:genetics* / Q000378:metabolism; D012907:Smoking; D019966:Substance-Related Disorders / Q000235:genetics / Q000378:metabolism
D043683:Receptors, Adenosine A2; D002110:Caffeine; D004247:DNA; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2