ORIGINAL CONTRIBUTION

EPIDEMIOLOGIC STUDIES EXAMIN-ing the association between cof-fee consumption and risk ofmyocardial infarction (MI) have been inconclusive.1-14 Coffee is a ma-jor source of caffeine (1,3,7-trimethyl-xanthine), which is the most widely consumed stimulant in the world and has been implicated in the develop-ment of cardiovascular diseases such as acute MI.15-17 However, coffee con-tains a number of other chemicals that have variable effects on the cardiovas-cular system.18 Because of the strong collinearity between caffeine intake and coffee consumption in many popula-tions, it is not clear whether caffeine alone affects the risk of MI or whether other chemicals found in coffeemay be responsible. Furthermore, the associa-tion between coffee consumption and unhealthy lifestyle factors suggests that previous associations might have been due to residual confounding.19 Caffeine is metabolized primarily by cytochromeP450 1A2 (CYP1A2) in the liver through an initial N3-demethyl-ation.20,21 CYP1A2 accounts for approxi-mately 95 % of caffeinemetabolism and demonstrates wide variability in en-zyme activity between individuals.21-23 An A→C substitution at position 734 (CYP1A2*1F) in the CYP1A2 gene de-creases enzyme inducibility as mea-sured by the ratio of plasma or urinary caffeine to caffeine metabolites after a dose of caffeine, resulting in impaired caffeinemetabolism.24-26 Carriers of the variantCYP1A2*1F allele are “slow ” caf-feine metabolizers, whereas individu-als who are homozygous for the CYP1A2*1A allele are “rapid ” caffeine metabolizers.24-26 The purpose of this study was to determine whether CYP1A2 genotype modifies the asso-ciation between intake of caffeinated coffee and risk of nonfatal MI