LACK OF RELATIONSHIP BETWEEN AN INSERTION DELETION POLYMORPHISM IN THE ANGIOTENSIN I-CONVERTING ENZYME GENE AND DIABETIC NEPHROPATHY AND PROLIFERATIVE RETINOPATHY IN IDDM PATIENTS

Genotypic abnormalities of the renin-angiotensin system have been sugg ested as a risk factor for the development of diabetic nephropathy and proliferative retinopathy. We studied the relationship between an ins ertion(I)/deletion (D) polymorphism in the angiotensin-converting enzy me (ACE) gene in insulin-dependent diabetes mellitus (IDDM) patients w ith diabetic nephropathy (121 men and 71 women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years) and in IDDM patients with normoalbu minuria (118 men and 74 women, age 42.7 +/- 10 years, diabetes duratio n 26 +/- 8 years). A total of 155 patients (40%) had proliferative ret inopathy, and 67 patients (17%) had no diabetic retinopathy. There was no difference in genotype distribution between IDDM patients with dia betic nephropathy and those with normoalbuminuria: 63 (32%)/95 (48%)/4 0 (20%) vs. 67 (35%)/77 (41%)/46 (24%) had DD/ID/II genotypes, respect ively. Patients with nephropathy had higher plasma ACE levels (609 [15 1-1,504] mu g/l) compared with patients with normoalbuminuria (428 [55 -1,630] mu g/l) (P < 0.001). Multiple linear regression analysis revea led that the plasma ACE level in patients with nephropathy is partiall y determined by ACE/ID polymorphism, mean arterial blood pressure, and glomerular filtration rate (r(2) = 0.30, P < 0.001). There was no dif ference in genotype distribution between IDDM patients with proliferat ive retinopathy and those without diabetic retinopathy: 52 (34%)/74 (4 8%)/29 (19%) vs. 26 (39%)/25 (37%)/16 (24%) had DD/ID/II genotypes, re spectively. There was also no difference in plasma ACE concentration d etected among patients with no, simplex, or proliferative retinopathy. We conclude that the ACE/ID polymorphism does not contribute to the g enetic susceptibility to diabetic nephropathy and proliferative retino pathy, whereas the raised plasma ACE concentration may play a role in the initiation and progression of diabetic nephropathy in Caucasian ID DM patients.