POLYMORPHISM OF ANGIOTENSIN-CONVERTING ENZYME, ANGIOTENSINOGEN, AND APOLIPOPROTEIN-E GENES IN A JAPANESE POPULATION WITH CEREBROVASCULAR-DISEASE

The homozygous deletion allele of the angiotensin converting enzyme ge ne (ACE/DD), homozygous threonine allele of the angiotensinogen gene ( AGN/TT), and the epsilon 4 allele of the apolipoprotein E gene (apoE/e psilon 4) are reported to be associated with ischemic heart disease. C erebrovascular disease (CVD) is another atherosclerotic disease; and t he effects of these polymorphisms on CVD have been confusing. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon 4 geno types are associated with CVD and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in pati ents with cerebral infarction (n = 55) and cerebral hemorrhage (n = 38 ), diagnosed by brain computed tomography. Control subjects for the in farction group and the hemorrhage group were randomly selected from 58 3 subjects matched for age, gender, and history of hypertension with p atients. Frequency of ACE/DD genotype was higher in the patients with infarction than in the controls (chi(2) = 6.1, P < .05). The AGN/TT ge notype was not associated with either infarction or hemorrhage, but it increased the relative risk for cerebral infarction in the subjects w ith ACE/DD genotype (chi(2) = 8.0, P < .01, odds ratio; 11.7, 95% conf idence intervals: 1.4 to 96.0). There was no significant association b etween apoE/epsilon 4 and CVD. These results suggest that ACE/DD predi cts cerebral infarction, but not cerebral hemorrhage, and that AGN/TT enhances the risk for cerebral infarction associated with ACE/DD. (C) 1997 American Journal of Hypertension, Ltd.