Tumor necrosis factor-alpha gene polymorphism in reflux nephropathy.

Abstract

Interstitial scarring contributes to the progression of renal failure in reflux nephropathy. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been implicated in the disease susceptibility and pathogenesis of several inflammatory diseases promoting interstitial infiltration of inflammatory cells. We evaluate the frequency of TNF-alpha gene polymorphism in patients with reflux nephropathy. Renal scarring was evaluated with technetium dimercapto-succinic acid renal scan. Genotyping was performed on 104 patients with reflux nephropathy and 30 controls for the TNF-alpha gene polymorphisms using polymerase chain reaction and restriction digest. This polymorphism involved a guanidine to adenosine transition at position -308 and was designated as TNF1 (-308G) and TNF2 (-308A). The allele frequencies of TNF1 and TNF2 were 18.8% and 81.2% in patients with reflux nephropathy and 76.7% and 23.3% in controls, respectively. The genotype distribution of TNF-alpha-AA was significantly higher (66.4% vs 10%, p <0.05), while the TNF-alpha-GG was lower (13.4% vs 60%, p <0.05) in patients with reflux nephropathy compared to controls. This study demonstrates for the first time the association of the cytokine TNF-alpha gene polymorphism in patients with reflux nephropathy. Our data suggest that patients with vesicoureteral reflux and TNF-alpha AA genotype may have increased susceptibility to reflux nephropathy.