TGF-β1 gene polymorphisms and primary vesicoureteral reflux in childhood

Abstract

The aim of this study was to assess the association between the transforming growth factor-beta1 (TGF-beta1) gene polymorphisms rs1800469 (commonly known as T-509C) and rs1982073 (commonly known as Leu (10)-->Pro) and primary vesicoureteral reflux (VUR) and renal scarring. Using a case-control approach, we examined 121 children with primary VUR and 169 controls. Genotyping of the TGF-beta1 gene polymorphisms was performed by restriction fragment length polymorphism (RFLP) analysis. The (99m)Tc-DMSA- or (99m)Tc-unitiol-single photon emission computed tomography method was used to evaluate renal scars in 84 of 121 VUR children. Statistical analysis revealed differences in rs1800469 genotype frequencies between VUR patients and controls (p = 0.0021). Our data demonstrate that individuals homozygous for the TT genotype are at risk of primary VUR [odds ratio (95% confidence interval) = 2.7 (1.46-5.08)]. Distribution of the rs1982073 polymorphism was similar in VUR children and controls. In terms of renal scarring, patients were stratified into non-scar and scar subgroups, and no differences in the genotype frequencies of either polymorphism was found. Previous reports have shown that the TT genotype of the rs1800469 polymorphism is a risk factor for renal scarring in primary VUR, and the results of our study suggest that this same polymorphism is associated with susceptibility to this congenital uropathy.

Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases

“…Valladares-Salgado et al 29 reported that TT genotype carriers of +869T/C polymorphism had lower cholesterol and triglycerides levels, and T allele carriers of +869 T/C polymorphism confer protection against diabetic nephropathy. Kowalewska-Pietrzak et al 30 reported that TT genotype carriers of À509 T/C polymorphism was a risk factor for renal scarring in primary vesicoureteral reflux (VUR), and was also associated with susceptibility to congenital uropathy. Yim et al 31 reported that TGF-b1 C-509T, G-800A, and T869C polymorphisms could be genetic markers of the process of urinary tract infection and VUR.…”

Post-Inflammatory Nephropathy

“…An association between polymorphism of angiotensin-converting enzyme gene and renal scarring was demonstrated (Haszon et al, 2002;Hohenfellner et al, 1999;Ohtomo et al, 2001;Ozen et al, 1999;Pardo et al, 2003). Similarly, polymorphism of transforming growth factor gene (Kowalewska-Pietrzak et al, 2008;Hussein et al, 2010) and polymorphism of vascular endothelium growth factor gene (Hussein et al, 2010) had impact on severity of renal scarring. Post-inflammatory nephropathy may be classified into reflux nephropathy due to vesicoureteral reflux and obstructive nephropathy due to urinary tract obstruction (Marra et al, 2004;Orikasa et al, 1995;Smellie et al, 1981).…”

“…Some studies questioned the significance of ACE gene polymorphism as an independent risk factor for the development and progression of RN (Dudley et al, 2002;Pardo et al, 2003). An association between TGF-1 gene polymorphism and the risk of renal scarring in patients with vesicoureteral reflux was also disclosed Kowalewska-Pietrzak et al (2008), whereas Hussein et al (2010) demonstrated an association between vascular endothelium growth factor (VEGF) gene polymorphism and the risk of the development of RN.…”

Genetic susceptibility to renal scar formation after urinary tract infection: a systematic review and meta-analysis of candidate gene polymorphisms

“…The HWE was assessed in seven studies [38,39,42,43,46,50,51]. Calculation disclosed that seven studies presented a significant deviation from HWE [32,41,42,48,[51][52][53].…”

“…Most studies (67%) did not give a sufficient description of how they diagnosed UTIs in their patients, whereas six studies reported that the UTIs were diagnosed based on clinical and laboratory investigations [32,38,39,42,43,51].…”