Angiotensin Converting Enzyme Gene Polymorphism in Asian Indian Children With Congenital Uropathies

Abstract

To evaluate the role of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism as a risk factor for progressive renal damage in Asian Indian children with congenital uropathies. ACE I/D polymorphism was determined by polymerase chain reaction in 84 children with congenital uropathies and 80 unrelated healthy controls. The study group included primary vesicoureteral reflux (29 patients), pelviureteral junction obstruction (21) and posterior urethral valves (34). Mean patient age was 69.4 +/- 4.5 months, and mean followup period was 7.2 +/- 1.5 years. Serum creatinine, ultrasound, voiding cystourethrogram and dimercaptosuccinic acid scans were done to evaluate renal function. The ACE I/D genotype distribution was similar in the 84 patients, II in 37 (44%), DI in 30 (35.7%) and DD in 17 (20.2%), and 80 controls, II in 36 (45%), DI in 30 (37.5%) and DD in 14 (17.5%), chi-square 0.00, p = 1.0). Renal scarring was seen in 49 of 84 patients (58.3%), with D allele present in 35 of 49 (71.4%), compared to 12 of 84 patients (34.2%) in the nonscarring group (chi-square 4.2, p = 0.02). Progressive scarring and renal failure were seen in 23 (27.3%) and 26 (31%) of patients, respectively, with D allele present in 21 of 23 (91.3%) and 21 of 26 (81%), respectively (chi-square 5.4, p = 0.001). Multivariate analysis showed that D allele is an independent risk factor for renal damage. The presence of D allele in I/D polymorphism of angiotensin converting enzyme gene is associated with progressive deterioration of renal function in congenital uropathies. The D allele was also significantly associated with renal scarring independent of known risk factors such as grade of reflux, age at diagnosis, gender and urinary tract infection.