Influence of insertion/deletion polymorphism in the ACE-I gene on the progression of diabetic glomerulopathy in type 1 diabetic patients with microalbuminuria

OBJECTIVE - To investigate the influence of the insertion/deletion polymorp hism of the ACE gene on the progression of early diabetic glomerulopathy in patients with and without antihypertensive treatment (AHT). RESEARCH DESIGN AND METHODS - There were 30 microalbuminuric patients with >5 years of type I diabetes who had renal biopsies taken at baseline and af ter 26-48 months of follow-up. Of the 30 patients, 13 (4 with II genotype a nd 9 with ID and DD genotypes) were randomized to AHT (enalapril or metopro lol) during the study The ACE genotype was determined by a polymerase chain reaction. Glomerular structural changes were measured by stereological met hods. RESULTS - Of the patients, 8 had the II genotype, 19 had ID genotype, and 3 had DD genotype. During the study, basement membrane thickness, matrix sta r volume, and the overall diabetic glomerulopathy index were increased in p atients with ID and DD genotypes only (P < 0.001, P = 0.01, P < 0.001, resp ectively). Among those with ID and DD genotypes, progression of basement me mbrane thickening and diabetic glomerulopathy index were increased in those without AHT, as compared with the antihypertensive treated patients (P < 0 .001, P = 0.02, respectively). In multivariate analysis, the ACE genotype h ad an independent influence on the progression of basement membrane thicken ing (P = 0.01), when AHT (P < 0.001) and the mean HbA(1c) during the study (P < 0.001) were also taken into account, ACE genotype tended to be indepen dently associated with the diabetic glomerulopathy index (P = 0.05). CONCLUSIONS - Microalbuminuric type 1 diabetic patients carrying the D-alle le have an increased progression of diabetic glomerulopathy. Presence of th is allele and no AHT seems to enhance this profess, larger studies are need ed to confirm the clinical significance of our findings.