Implications of certain genetic polymorphisms in scarring in vesicoureteric reflux: Importance of ACE polymorphism

Polymorphisms of the renin-angiotensin system (RAS) have been shown to affe ct renal prognosis In a number of diseases. We examined the influence of de letion (D) and insertion (I)polymorphism in the angiotensin I-converting en zyme (ACE) gene and the other polymorphic markers of RAS, and that of plasm inogen-activator inhibitor-1 (PAI-1) on renal scarring in reflux nephropath y. Ninety-four children with third- or fourth-degree reflux were the subjec t of the study. They were stratified Into two groups according to the techn etium-99m-dimercaptosuccinic acid (DMSA) findings: the first group consiste d of 41 patients with no scar formation. In the second group (n = 53), ther e was significant scar formation In the refluxing units. ACE levels, ACE ge ne, angiotensin-l receptor (AT1) A1166C, angiotensinogen (ATG) M235T, and P AI-I 4G/5G polymorphisms were studied. In the second group with scarred kid neys, 18 patients had decreased renal function. The frequency of patients h omozygous for the D allele was significantly greater in the second group wi th scar formation in the refluxing units compared with the first group of p atients (P < 0.005). On multivariate analysis, the DD genotype was the only factor that had a significant impact on renal scar formation, introducing a 4.9-fold risk (P < 0.05, 95% confidence interval). We were unable to find any correlation with the presence of DD genotype and hypertension, decreas ed renal function, proteinuria, or sex of the patient. DD genotype correlat ed with the serum ACE levels (P < 0.005). An and ATG polymorphisms and PAI- 1 polymorphism did not correlate with scar formation or any of the paramete rs. This study provides evidence that the DD genotype of ACE may be a genet ic susceptibility factor contributing to adverse renal prognosis In reflux nephropathy; namely, scar formation. The role of the synergism between the aforementioned genetic polymorphisms can be enlightened with larger patient groups, possibly through multicenter studies. (C) 1999 by the National Kid ney Foundation, Inc.