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 associa ted with an increase in the incidence of ischemic heart disease. In th is study, we examined whether the apolipoprotein epsilon 4 genotype an d angiotensin-converting enzyme/DD allele are associated with silent m yocardial ischemia. We screened 3920 subjects undergoing general check ups who had no symptoms of ischemic heart disease. Seventy subjects (2 %) showed ischemic ST-segment depression during the double two-step ex ercise test. One hundred and twenty control subjects without ischemic ST-segment depression were recruited from the same population and matc hed for sex, age, aad blood pressure. We performed genotyping of the a polipoprotein E gene (epsilon 2, epsilon 3, and epsilon 4) and angiote nsin-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 b etween the allele or the genotype frequency of the angiotensin-convert ing enzyme gene and the incidence of ischemic ST-segment depression. F urthermore, stepwise multiple regression analysis also revealed that t otal cholesterol level and epsilon 4 genotype were predictors of ische mic change in the exercise tolerance lest (chi(2)=12.8, P<.005, R(2)=. 051). These results suggest that the apolipoprotein epsilon 4 allele i s an independent genetic risk factor for silent myocardial ischemia in Japanese subjects.