INSERTION DELETION POLYMORPHISM OF THE ANGIOTENSIN-CONVERTING ENZYME GENE IS STRONGLY ASSOCIATED WITH CORONARY HEART-DISEASE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS/

Non-insulin-dependent diabetes mellitus (NIDDM) is considered a model of premature atherosclerosis with a strong genetic component. We have investigated the role of angiotensin-converting enzyme (ACE; EC 3.4.15 .1) gene in 316 unrelated NIDDM individuals, 132 who had myocardial in farction or significant coronary stenoses and 184 with no history of c oronary heart disease (CHD). A deletion-polymorphism in the ACE gene w as recently reported to be associated with myocardial infarction espec ially in people classified as low risk. Here we report that the D alle le of the ACE gene is a strong and independent risk factor for CHD in NIDDM patients. The D allele is associated with early-onset CHD in NID DM, independently of hypertension and lipid values. A progressively in creasing relative risk in individuals heterozygous and homozygous for the D allele was observed (odds ratios of 1.41 and 2.35, respectively; P < 0.007), suggesting a codominant effect on the cardiovascular risk . The percentage of CHD attributable to the ACE deletion allele was 24 % in this NIDDM population. Identification of NIDDM patients carrying this putative CHD-susceptibility genotype would help early detection a nd treatment of CHD.