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

Background: The activation of the renin-angiotensin system in various renal disorders is well established. Congenital urological abnormalities, such a s obstruction and reflux, are common causes of renal failure in children co ntributing to approximately 25% of chronic renal failure in this age group. While the outlook relates to the severity of initial renal damage, there i s considerable heterogeneity in renal parenchymal destruction among individ uals and the reasons for this heterogeneity are not fully understood. A pol ymorphism 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 h ave determined the incidence of this ID polymorphism of the ACE gene in 47 Kuwaiti children with different urological abnormalities leading to variabl e degrees of renal impairment and in 48 healthy control subjects with a sim ilar ethnic background. Methods: 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. Results: 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 homozygou s II genotype was detected in 6/47 (13%) cases compared with 1/48 (2%) cont rols (P=0.0247). The D allele of ACE gene was detected in 41/47 (87%) uropa thy cases when individuals with homozygous DD and heterozygous ID genotypes were considered collectively. The incidence of parenchymal damage was cons iderably higher in uropathy cases with DD genotype (62%) compared with thos e having ID (26%) and II (12%) genotypes. Conclusions: Our data suggest an association of D allele of the ACE gene in sertion/deletion polymorphism and congenital urological abnormalities, whic h result in parenchymal damage in Kuwaiti Arab children.