ANGIOTENSIN-I CONVERTING-ENZYME GENE POLYMORPHISM IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

A total of 168 patients with non-insulin dependent diabetes (NIDDM) fo llowed over 10 years were recruited in this study. The patients were d ivided into two groups: Group 1 patients had a stable renal function ( N = 96) and Group 2 had a declining renal function (N = 72). Group 1 i ncluded those whose serum creatinine was normal five years ago but had increased to greater than or equal to 2 mg/dl or those who has reache d end-stage renal failure (requiring dialysis) by the time of study. A ll patients were genotyped for the insertion/deletion (I/D) polymorphi sm of the ACE gene, the M235T polymorphism of the angiotensinogen (Atg ) gene and the A1166C polymorphism of the angiotensin II type 1 recept or (AT1) gene. The genotype frequency distributions of M235T Atg and t he A116C AT1 gene polymorphisms were not different between Group 1 ver sus Group 2. While the frequency of the ACE DD genotype in Group 1 (7. 3%) was comparable to that of the general population, the DD frequency was significantly higher in Group 2 (26.4%) than in Group 1 (odds rat io, 4.56; 95% confidence interval, 1.80 similar to 11.56, P < 0.001). Among all 165 patients studied, the renal survival rate was significan tly lower among DD than ID (P < 0.005) or II patients (P < 0.001). In patients with a declining renal function (Group 2), those with the DD genotype had a significantly shorter time interval from onset of diabe tes to the initiation of dialysis (13.4 +/- 1.4 years) than those with ID (20.7 +/- 1.2 years, P < 0.01) or II genotypes (17.5 +/- 1.1 year, P < 0.01). Analysis of the clinical course of the three ACE genotypes revealed that the majority (95%) of patients with the DD genotype who had albuminuria progressed to end-stage renal disease within 10 years of diagnosis of diabetes. Our analysis also revealed that initiation and continuation of dialysis are associated with a progressive decreas e in the frequency of the DD genotype. These results indicate that, in NIDDM, the ACE DD genotype has a high prognostic value for progressiv e deterioration of renal function. Moreover, the DD genotype appears t o increase the mortality once dialysis is initiated.