Angiotensin-converting enzyme gene insertion/deletion polymorphism and renal damage in childhood uropathies.

Abstract

The activation of the renin-angiotensin system in various renal disorders is well established. Congenital urological abnormalities, such as obstruction and reflux, are common causes of renal failure in children contributing to approximately 25% of chronic renal failure in this age group. While the outlook relates to the severity of initial renal damage, there is considerable heterogeneity in renal parenchymal destruction among individuals and the reasons for this heterogeneity are not fully understood. A polymorphism within intron 16 of the angiostensin-converting enzyme (ACE) gene has been shown to influence the activity of the renin-angiotensin system, thus, it may also have an impact on the expression of renal disorders. We have determined the incidence of this ID polymorphism of the ACE gene in 47 Kuwaiti children with different urological abnormalities leading to variable degrees of renal impairment and in 48 healthy control subjects with a similar ethnic background. Blood samples were collected from the patients (n = 47) and controls (n = 48), total genomic DNA extracted and the ACE genotypes were determined using a polymerase chain reaction-based method. The DD genotype was detected in 27/47 (57%) cases compared with 25/48 (52%) controls (P = 0.439). The heterozygous genotype ID was found in 14/47 (29%) cases compared with 22/48 (46%) controls (P = 0.0138). The homozygous II genotype was detected in 6/47 (13%) cases compared with 1/48 (2%) controls (P = 0.0247). The D allele of ACE gene was detected in 41/47 (87%) uropathy cases when individuals with homozygous DD and heterozygous ID genotypes were considered collectively. The incidence of parenchymal damage was considerably higher in uropathy cases with DD genotype (62%) compared with those having ID (26%) and II (12%) genotypes. Our data suggest an association of D allele of the ACE gene insertion/deletion polymorphism and congenital urological abnormalities, which result in parenchymal damage in Kuwaiti Arab children.