ORIGINAL CONTRIBUTION Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction

EPIDEMIOLOGIC STUDIES EXAMINing the association between coffee consumption and risk of myocardial infarction (MI) have been inconclusive. Coffee is a major source of caffeine (1,3,7-trimethylxanthine), which is the most widely consumed stimulant in the world and has been implicated in the development of cardiovascular diseases such as acute MI. However, coffee contains a number of other chemicals that have variable effects on the cardiovascular system. Because of the strong collinearity between caffeine intake and coffee consumption in many populations, it is not clear whether caffeine alone affects the risk of MI or whether other chemicals found in coffee may be responsible. Furthermore, the association between coffee consumption and unhealthy lifestyle factors suggests that previous associations might have been due to residual confounding. Caffeine is metabolized primarily by cytochrome P450 1A2 (CYP1A2) in the liver through an initial N-demethylation. CYP1A2 accounts for approximately 95% of caffeine metabolism and demonstrates wide variability in enzyme activity between individuals. An A→C substitution at position 734 (CYP1A2*1F) in the CYP1A2 gene decreases enzyme inducibility as measured by the ratio of plasma or urinary caffeine to caffeine metabolites after a dose of caffeine, resulting in impaired caffeine metabolism. Carriers of the variant CYP1A2*1F allele are “slow” caffeine metabolizers, whereas individuals who are homozygous for the CYP1A2*1A allele are “rapid” caffeine metabolizers. The purpose of this study was to determine whether CYP1A2 genotype modifies the association between intake of caffeinated coffee and risk of nonfatal MI.