INSERTION DELETION POLYMORPHISM IN THE ANGIOTENSIN-I-CONVERTING ENZYME GENE IS ASSOCIATED WITH CORONARY HEART-DISEASE IN IDDM PATIENTS WITHDIABETIC NEPHROPATHY

Insulin-dependent diabetic (IDDM) patients with diabetic nephropathy h ave a highly increased morbidity and mortality from coronary heart dis ease. An insertion (I) /deletion (D) polymorphism in the angiotensin-I -converting enzyme (ACE) gene has been shown to be associated with cor onary heart disease. Therefore, we have investigated the role of this ACE/ID polymorphism in 198 IDDM patients with diabetic nephropathy and 190 normoalbuminuric IDDM patients. The prevalence of myocardial infa rction and other coronary heart disease was significantly elevated in patients with nephropathy, 19 % (38/198) vs 8 % (15/190), p < 0.001. I n the nephropathic group 12 of 63 (19 %), 23 of 95 (24 %), and 3 of 40 (7.5 %) patients with the DD, ID and II genotypes, respectively had a history of coronary heart disease, II vs DD and ID, p < 0.05 when com pared to nephropathic patients without coronary heart disease. Multipl e logistic regression analysis of the risk factors associated with cor onary heart disease in univariate analysis revealed that the II genoty pe acts as an independent protective factor against coronary heart dis ease, odds ratio II/DD + ID 0.27 (95 % confidence interval 0.07-0.97, p < 0.05). There was no difference in genotype or allele frequency (D/ I) between patients with and without nephropathy, 0.56/0.44 in both gr oups, but plasma ACE concentration was elevated in patients with nephr opathy 609 (151-1504) ng/ml as compared to patients with normoalbuminu ria, 428 (55-1639) ng/ml, p < 0.001. We suggest that ACE/ID polymorphi sm may influence the frequency of life-threatening cardiac complicatio ns in IDDM patients suffering from diabetic nephropathy, a condition c haracterized by increased plasma ACE concentration.