Coffee, CYP1A2 genotype, and risk of myocardial infarction.
BACKGROUND
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.


OBJECTIVE
To determine whether CYP1A2 genotype modifies the association between coffee consumption and risk of acute nonfatal MI.


METHODS
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.


METHODS
Relative risk of nonfatal MI associated with coffee intake, calculated using unconditional logistic regression.


RESULTS
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).


CONCLUSIONS
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.
Cornelis
Marilyn C
MC
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
El-Sohemy
Ahmed
A
Kabagambe
Edmond K
EK
Campos
Hannia
H
D000368:Aged; D019943:Amino Acid Substitution; D002391:Catchment Area, Health; D003069:Coffee / Q000009:adverse effects*; D003364:Costa Rica; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D003069:Coffee; D019388:Cytochrome P-450 CYP1A2