ACE and PC-1 gene polymorphisms in normoalbuminuric Type 1 diabetic patients -: A 10-year prospective study

The aim of this study was to analyze the role of ACE gene insertion/deletion (I/D) and PC-1 gene K121Q polymorphisms in the changes of glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and blood pressure (BP) levels in a cohort of normoalbuminuric Type 1 diabetic patients. This is a 10.2 +/- 2.0-year prospective study of 30 normotensive normoalbuminuric Type 1 diabetic patients. UAER (immunoturbidimetry), GFR (Cr-51-EDTA single injection technique), GHb (ion exchange chromatography), and BP levels were measured at baseline and at 1.7 +/- 0.6-year intervals. The presence of ACE gene I/D and PC-I gene K121Q polymorphisms was determined by polymerase chain reaction (PCR) and restriction enzyme techniques. Three patients developed diabetic nephropathy (DN), all carriers of allele D. The presence of allele D was the only predictor (R-2 = .15, F = 4.92, P = .035) of the observed GFR decline (-0.29 +/- 0.34 ml/min/month, P < .05). UAER increased during the study (log UAER = 0.0275 +/- 0.042 mug/min/month, P = .002) and was associated with baseline UAER levels only (R-2 = .17, F = 5.72, P = .024). A significant increase (P < .05) in cases of hypertension and retinopathy were observed in ID/DD (n = 19) and not in 11 patients (n = 11). Patients with the KQ/QQ genotype (n = 8) presented a significant increase (P = .045) in new cases of retinopathy. In conclusion, the presence of the ACE gene D allele in this sample of normoalbuminuric normotensive Type 1 diabetic patients was associated with a higher proportion of microvascular complications and hypertension. (C) 2002 Elsevier Science Inc. All rights reserved.