The association between coffee intake and risk of myocardial infarction (MI) remains
controversial. Coffee is a major source of caffeine, which is metabolized by the polymorphic
cytochrome P450 1A2 (CYP1A2) enzyme. Individuals who are homozygous for the CYP1A2*1A
allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F
are "slow" caffeine metabolizers.
To determine whether CYP1A2 genotype modifies the association between coffee consumption
and risk of acute nonfatal MI.
Cases (n = 2014) with a first acute nonfatal MI and population-based controls (n =
2014) living in Costa Rica between 1994 and 2004, matched for age, sex, and area of
residence, were genotyped by restriction fragment-length polymorphism polymerase chain
reaction. A food frequency questionnaire was used to assess the intake of caffeinated
coffee.
Relative risk of nonfatal MI associated with coffee intake, calculated using unconditional
logistic regression.
Fifty-five percent of cases (n = 1114) and 54% of controls (n = 1082) were carriers
of the slow *1F allele. For carriers of the slow *1F allele, the multivariate-adjusted
odds ratios (ORs) and 95% confidence intervals (CIs) of nonfatal MI associated with
consuming less than 1, 1, 2 to 3, and 4 or more cups of coffee per day were 1.00 (reference),
0.99 (0.69-1.44), 1.36 (1.01-1.83), and 1.64 (1.14-2.34), respectively. Corresponding
ORs (95% CIs) for individuals with the rapid *1A/*1A genotype were 1.00, 0.75 (0.51-1.12),
0.78 (0.56-1.09), and 0.99 (0.66-1.48) (P = .04 for gene x coffee interaction). For
individuals younger than the median age of 59 years, the ORs (95% CIs) associated
with consuming less than 1, 1, 2 to 3, or 4 or more cups of coffee per day were 1.00,
1.24 (0.71-2.18), 1.67 (1.08-2.60), and 2.33 (1.39-3.89), respectively, among carriers
of the *1F allele. The corresponding ORs (95% CIs) for those with the *1A/*1A genotype
were 1.00, 0.48 (0.26-0.87), 0.57 (0.35-0.95), and 0.83 (0.46-1.51).
Intake of coffee was associated with an increased risk of nonfatal MI only among individuals
with slow caffeine metabolism, suggesting that caffeine plays a role in this association.