TUMOR NECROSIS FACTOR-α GENE POLYMORPHISM IN REFLUX NEPHROPATHY

ABSTRACT 

Purpose:

Interstitial scarring contributes to the progression of renal failure in reflux nephropathy. The proinflammatory cytokine tumor necrosis factor-α (TNF-α) 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-α gene polymorphism in patients with reflux nephropathy.

Material and Methods:

Renal scaring was evaluated with ⁹⁹technetium dimercapto-succinic acid renal scan. Genotyping was performed on 104 patients with reflux nephropathy and 30 controls for the TNF-α 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).

Results:

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-α-AA was significantly higher (66.4% vs 10%, p <0.05), while the TNF-α-GG was lower (13.4% vs 60%, p <0.05) in patients with reflux nephropathy compared to controls.

Conclusions:

This study demonstrates for the first time the association of the cytokine TNF-α gene polymorphism in patients with reflux nephropathy. Our data suggest that patients with vesicoureteral reflux and TNF-α AA genotype may have increased susceptibility to reflux nephropathy.

Key Words::  tumor necrosis factor , polymorphism genetics , kidney nephropathy , vesico-ureteral reflux