RELATIONSHIPS BETWEEN ANGIOTENSIN-I CONVERTING-ENZYME GENE POLYMORPHISM, PLASMA-LEVELS, AND DIABETIC RETINAL AND RENAL COMPLICATIONS

Insulin-dependent diabetes mellitus (IDDM), cardiovascular morbidity, and vital prognosis are linked to diabetic nephropathy, which is proba bly determined by renal hemodynamic abnormalities and by a genetic pre disposition. Angiotensin I converting enzyme (ACE) regulates systemic and renal circulations through angiotensin II formation and kinins met abolism. Plasma and cellular ACE levels are genetically determined; an insertion/deletion polymorphism of the ACE gene is strongly associate d with ACE levels, subjects homozygote for insertion (genotype II) hav ing the lowest plasma values. We studied the relationship between the ACE gene polymorphism or plasma levels and microcirculatory disorders of IDDM through two independent studies: one involved 57 subjects with or without diabetic retinopathy, and the other compared 62 IDDM subje cts with diabetic nephropathy to 62 diabetic control subjects with the same characteristics (including retinopathy severity) but with normal kidney function. The ACE genotype distribution was not different in d iabetic subjects with or without retinopathy and in a healthy populati on. Conversely, an imbalance of ACE genotype distribution, with a low proportion of II subjects, was observed in IDDM subjects with diabetic nephropathy compared with their control subjects (P = 0.006). Plasma ACE levels were mildly elevated in all diabetic groups, independently of retinopathy, but they were higher in subjects with nephropathy than in those without nephropathy (P = 0.0022). The II genotype of ACE gen e is a marker for reduced risk for diabetic nephropathy.