Genetic Control of VEGF and TGF-β1 Gene Polymorphisms in Childhood Urinary Tract Infection and Vesicoureteral Reflux

Abstract

We investigated whether genetic polymorphisms of vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1), potential candidate genes in the pathogenesis of urinary tract infection (UTI) and vesicoureteral reflux (VUR), are associated with the susceptibility to UTI and VUR, and renal scarring. We recruited 89 controls and 86 UTI and 58 VUR children. The UTI group was subdivided into two groups according to renal scarring. Two polymorphisms of VEGF and three of TGF-beta1 genes were investigated by using PCR-restriction fragment length polymorphism analysis. In both UTI and VUR groups, there was an increase in frequency of the VEGF -460 CC (control, 4.3; UTI, 15.9; VUR, 17.8%; p < 0.05), TGF-beta1 -509 CC (control, 8.7; UTI, 34.6; VUR, 35.1%; p < 0.001), and TGF-beta1 -800 GG genotypes (control, 19.1; UTI, 40.5; VUR, 40.4%; p < 0.05). An increase in the TGF-beta1 +869 CC (scar-positive, 35.4; scar-negative, 10.3%; p < 0.05) and a decrease in the +869 TC genotype (scar-positive, 29.2; scar-negative, 55.2%; p < 0.05) were observed in the scar-positive subjects. There were no differences in +405 VEGF genotype frequencies. The VEGF T-460C and the TGF-beta1 C-509T, G-800A, and T869C polymorphisms could be genetic markers of the process of UTI and VUR.