Apolipoprotein E genotype: epsilon32 women are protected while epsilon43 and epsilon44 men are susceptible to ischemic heart disease: The Copenhagen City Heart Study

OBJECTIVES We tested the hypothesis that risk of ischemic heart disease (IHD) differs as a function of apolipoprotein E (APOE) genotype in women and men. BACKGROUND Apolipoprotein E genotype influences lipids and lipoproteins and, therefore, possibly the risk of IHD. METHODS We genotyped 9,241 white women and men from the general population and 940 white women and men with IHD. RESULTS Test of interaction suggested that APOE genotype may influence risk of IHD differently in women and men (p = 0.07). After age adjustment, the odds ratio (OR) for IHD for epsilon32 versus epsilon33 women was 0.57 (95% confidence interval [CI]: 0.35 to 0.94) while epsilon43 and epsilon44 versus epsilon33 men had ORs of 1.16 (0.96 to 1.41) and 1.58 (1.01 to 2.45). After adjustment for age and other conventional cardiovascular risk factors, the equivalent ORs were for epsilon32 women 0.38 (0.18 to 0.79), for epsilon43 men 1.35 (1.02–1.78) and for epsilon44 men 1.58 (0.80 to 3.08). Equivalent ORs for epsilon43 and epsilon44 versus epsilon33 women and for epsilon32 versus epsilon33 men were all close to 1.0 and nonsignificant. Of the total risk of IHD relative to the epsilon33 genotype, the fraction attributed to epsilon32 in women was −9%, while the fractions attributed to epsilon43 and epsilon44 in men were +8% and +2%. CONCLUSIONS Relative to epsilon33 individuals, epsilon32 women are protected while epsilon43 and epsilon44 men are particularly susceptible to IHD.