title: Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption.
abstract: 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.
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Canada.
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Cornelis
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Sohemy
authors.forename: Hannia
authors.initials: H
authors.lastname: Campos
mesh_terms: 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
chemical_list: D043683:Receptors, Adenosine A2; D002110:Caffeine; D004247:DNA; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2