A prospective study of the association between APOE genotype and the risk of myocardial infarction among apparently healthy men

Background: Apolipoprotein E (apoE) plays an important role in lipid metabolism. Three common alleles in the APOE gene, E2/ E3/E4, have been associated with lipoprotein disorders but their effects on myocardial infarction (MI) risk remain uncertain. Methods: In a prospective cohort of 14 916 apparently healthy men enrolled in the Physicians' Health Study, APOE genotyping was conducted to determine three common alleles (E2/E3/E4) among 385 incident cases of first MI and among 373 age- and smoking-matched controls. Results: No significant differences in allele or genotype frequency for the APOE gene were detected between cases and controls. As expected, we observed significant positive associations between dyslipidemia (low HDL/high TG or high LDL) and MI risk (P < 0.001) and between genotypes and levels of LDL (P < 0.001), HDL (P = 0.04) or TG (P = 0.02). Compared with men homozygous for the E3 allele and after adjusting for multiple MI risk factors, men carrying the E4 allele (E4/4 or E4/3) had a relative risk of 0.93 (95% CI 0.63-1.37) and men carrying the E2 allele (E2/2 or E2/3) a relative risk of 1.03 (0.62-1.74). Moreover, no significant difference in MI risk was observed among different genotypes across different levels of lipids or smoking status. Conclusions: These data from a prospective study of apparently healthy men do not support the simple view of E2 as a protective factor and E4 as a susceptibility factor in predicting future risk of MI independent of lipid parameters. Nor did we observe any interaction between smoking and apoE4 allele on MI risk. (C) 2002 Elsevier Science Ireland Ltd, All rights reserved.