Polymorphism of the apolipoprotein E and angiotensin-converting enzyme genes in Japanese subjects with silent myocardial ischemia

The apolipoprotein epsilon 4 allele and homozygous deletion allele (DD) of the angiotensin-converting enzyme gene are reported to be associated with an increase in the incidence of ischemic heart disease. In this study, we examined whether the apolipoprotein epsilon 4 genotype and angiotensin-converting enzyme/DD allele are associated with silent myocardial ischemia. We screened 3920 subjects undergoing general checkups who had no symptoms of ischemic heart disease. Seventy subjects (2%) showed ischemic ST-segment depression during the double two-step exercise test. One hundred and twenty control subjects without ischemic ST-segment depression were recruited from the same population and matched for sex, age, aad blood pressure. We performed genotyping of the apolipoprotein E gene (epsilon 2, epsilon 3, and epsilon 4) and angiotensin-converting enzyme gene (I and D) using polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction, respectively. Allele frequency of epsilon 4 of the apolipoprotein E gene was higher in the ischemic group (11%) than the nonischemic group (5%) (chi(2)=5.35, P<.05), but there was no significant association between the allele or the genotype frequency of the angiotensin-converting enzyme gene and the incidence of ischemic ST-segment depression. Furthermore, stepwise multiple regression analysis also revealed that total cholesterol level and epsilon 4 genotype were predictors of ischemic change in the exercise tolerance lest (chi(2)=12.8, P<.005, R(2)=.051). These results suggest that the apolipoprotein epsilon 4 allele is an independent genetic risk factor for silent myocardial ischemia in Japanese subjects.