Renin-angiotensin system polymorphisms in Taiwanese primary vesicouretenal reflux

We studied the angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1R) gene polymorphisms for association with susceptibility to primary vesicoureteral reflux (VUR) and disease progression in 74 Taiwanese children, including 16 with end-stage renal disease (ESRD), and 117 normal controls. Polymerase chain reaction-amplified products containing the ACE gene T-5491C, A-5466C, T-3892C, A-3692C, A-240T, Alu I/D, the AGT gene C-532T, G-217A, G-152A, A-20C, A-6G, T174M, T235M, and the AT1R gene A-1138T, T-810A, T-713G, C-521T, AG-214CC, A-153G, A1166C polymorphisms were analyzed by restriction enzyme digestion, gel electrophoresis, or single-strand conformation polymorphism analysis. All the polymorphisms examined were in Hardy-Weinberg equilibrium. The strong non-random association within the ACE, AGT, and AT1R genes suggests low levels of intragenic recombination. None of these polymorphisms showed association with VUR susceptibility. However, the allele frequency distribution of the six ACE polymorphisms among primary VUR patients with or without ESRD was statistically different. The linked ACE T-A-T-A-A-I allele was observed significantly more frequently in VUR children with ESRD (P<0.001). A significant increase of left ventricular mass index was also found in the linked ACE T-A-T-A-A-I allele group compared with the non-ACE T-A-T-A-A-I allele group of patients aged 18 years with renal progression. The AGT A-6G genotype frequencies were significantly different when the analysis was stratified by genotype of the ACE polymorphisms. The data showed that ACE gene polymorphisms were associated with progressive renal deterioration in Taiwanese children with VUR and might act synergistically with the -6 G allele of the AGT gene.