Association of transforming growth factor-beta1 gene polymorphism with reflux nephropathy

Reflux nephropathy (RN) is recognized as a major cause of end stage renal failure in children and young adults. Transforming growth factor-beta1 (TGF-beta1) is a potent proinflammatory and fibrogenetic cytokine known to have a key role in the regulation of renal tissue fibrosis. We investigate genotype frequencies for polymorphisms of the TGF-beta1 gene at position -509, codon 10 and 25, and examine circulating levels of TGF-beta1 in patients with reflux nephropathy.

Renal scaring was evaluated with 99technetium dimercapto-succinic acid renal scan. Genotyping was performed in 123 patients with severe to moderate reflux nephropathy and 58 controls for the position -509, the coding region at position 10 and 25 of the TGF-beta1 gene polymorphisms by polymerase chain reaction, gel analysis and appropriate restriction digest. TGF-beta1 serum levels were measured with standard ELISA technique.

The genotype distribution of -509-CT was significantly increased in the RN group compared to controls, (82% vs 37%). Similarly, there was a significant increase in the CC Lue(10)-->Pro (codon 10) genotype (77% vs 27.5%, p <0.05), while TC Lue(10)-->Pro was significantly lower (7.3% vs 43%, p <0.05) in patients compared to controls. There was no significant difference in the Arg(25)-->Pro (codon 25) TGF-beta1 genotypes distribution between patients and controls. There were no statistically significant differences in the serum levels of TGF-beta1 in children with RN (4.2 +/- 0.3 mIU/ml) compared to controls (3.9 +/- 0.4 mIU/ml) (p >0.05).

Patients with TGF-beta1 -509 and Lue(10)-->Pro gene polymorphisms may be at higher risk for reflux nephropathy.