Enhanced Predictability of Myocardial Infarction in Japanese by Combined Genotype Analysis

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Abstract
Abstract To explore the genes responsible for myocardial infarction and restenosis after percutaneous transluminal coronary angioplasty, we performed association studies of the polymorphisms of the angiotensinogen and angiotensin-converting enzyme (ACE) genes. In the first study, normotensive myocardial infarction patients (n=103) and control subjects (n=103), who were matched for established risk factors with the myocardial infarction patients, were randomly selected. The angiotensinogen- TT genotype ( T indicates threonine instead of methionine at position 235) was more frequent in the myocardial infarction group than in the control group ( P <.05). The ACE- DD genotype ( D indicates a deletion polymorphism in intron 16) was also more frequent in the myocardial infarction group ( P <.0001). The odds ratio estimated by the combined analysis of the angiotensinogen- TT and ACE- DD genotypes (11.2) was markedly increased compared with that estimated separately from the angiotensinogen- TT (1.75) or ACE- DD (4.43) genotype. In the second study, we investigated 91 consecutive patients with acute myocardial infarction who underwent successful direct angioplasty. Combined analysis showed that the angiotensinogen- TT genotype did not enhance the predictability of myocardial infarction from the ACE- DD genotype. In conclusion, the angiotensinogen- TT genotype is a predictor for myocardial infarction, as well as the ACE- DD genotype, and the combined analysis of the angiotensinogen- TT and ACE- DD genotypes further enhanced the predictability of myocardial infarction in Japanese, suggesting its future clinical usefulness.