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  • Title: Association of transforming growth factor-beta1 gene polymorphism with familial vesicoureteral reflux.
    Author: Kuroda S, Solari V, Puri P.
    Journal: J Urol; 2007 Oct; 178(4 Pt 2):1650-3. PubMed ID: 17707032.
    Abstract:
    PURPOSE: Familial clustering of vesicoureteral reflux suggests that genetic factors have an important role in the pathogenesis of vesicoureteral reflux. Transforming growth factor-beta1 is a multifunctional peptide that controls proliferation and differentiation in many cell types. Recently an association between the transforming growth factor-beta1 -509 and +869 gene polymorphism, and renal parenchymal scarring was reported. We investigated the genetic contribution of transforming growth factor-beta1 in familial vesicoureteral reflux by examining the genotype frequencies of transforming growth factor-beta1 polymorphic variants. MATERIALS AND METHODS: The study included 141 families in which 1 or more siblings had primary vesicoureteral reflux. Renal parenchymal scarring was assessed using dimercapto-succinic acid scans. Genotyping was performed in 280 patients with vesicoureteral reflux, including 133 index patients and 147 siblings, and in 74 controls for the position -509 and the coding region at position 10 (+869) of the transforming growth factor-beta1 gene polymorphism by polymerase chain reaction, gel analysis and appropriate restriction digest. RESULTS: The genotype frequency of -509CC was significantly increased in the familial vesicoureteral reflux group compared to controls (58% vs 33%, p <0.01), whereas -509TT genotype frequency was significantly lower in the familial vesicoureteral reflux group compared to controls (7.5% vs 28%, p <0.01). Similarly there was a significant increase in the +869TT genotype (52% vs 32%, p <0.05), while the +869CC genotype was significantly lower in patients with familial vesicoureteral reflux compared to controls (11% vs 24%, p <0.01). There were no significant differences in transforming growth factor-beta1 genotype distribution between patients with vesicoureteral reflux with and without renal parenchymal scarring. CONCLUSIONS: To our knowledge this study demonstrates for the first time the association of the cytokine transforming growth factor-beta1 gene polymorphism in patients with familial vesicoureteral reflux. Individuals with the transforming growth factor-beta1 -509CC and 869TT genotype may have increased susceptibility to vesicoureteral reflux.
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