DELETION POLYMORPHISM OF THE ANGIOTENSIN I-CONVERTING ENZYME GENE IS ASSOCIATED WITH SERUM ACE CONCENTRATION AND INCREASED RISK FOR CAD IN THE JAPANESE

Background The angiotensin I-converting enzyme (ACE) is a key componen t of the renin-angiotensin system thought to be important in the patho genesis of hypertension and cardiovascular disease. Deletion polymorph ism in the ACE gene may be a risk factor for myocardial infarction in the Caucasian population. However, this finding has not yet been inves tigated in the Japanese population. Methods and Results A 287-bp inser tion/deletion polymorphism in intron 16 of the ACE gene was examined b y polymerase chain reaction in a cross-sectional study of 100 healthy subjects and 178 patients with coronary artery disease (CAD) (70 angin a pectoris, 108 myocardial infarction), whose serum ACE levels were co ncomitantly measured. Polymorphism of the ACE gene was characterized b y three genotypes: two deletion alleles (genotype DD), two insertion a lleles (genotype II), and heterozygous alleles (genotype ID), No diffe rences could be detected among the three genotypes for total cholester ol, HDL cholesterol, and body mass index. Serum ACE levels were 11.4+/ -2.7, 14.5+/-3.5, and 16.6+/-4.6 IU/mL for genotypes II, ID, and DD, r espectively. In the study population, the genotype DD was more closely associated with CAD than the other two genotypes (ID and II). The fre quency of deletion alleles was higher (0.58) in the CAD group than in healthy control subjects (0.42) (P<.05). Furthermore, multivessel dise ase was more strongly associated with deletion alleles than with inser tion alleles (P<.05). Conclusions A deletion polymorphism of the ACE g ene is associated with serum ACE activity and increased risk for CAD i n the Japanese.