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 14916 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.