Association of TGF-β1 polymorphisms with chronic renal disease

Background: Transforming growth factor beta1 (TGF-β1) plays an important role in tissue fibrosis and has been found to participate in cardiovascular disease (CVD). This study aimed to evaluate the association of TGF-β1 polymorphisms with chronic renal disease (CRD), and its progression to dialysis in a retrospective longitudinal study of an endstage renal disease (ESRD) cohort. Methods: The Arg/Pro (codon 25) and Leu/Pro (codon 10) polymorphisms were genotyped in 104 ESRD patients aged 64 ± 14 yrs (mean ± SD), 62 males, and in 104 matched controls. Results: The genotype distribution of Leu10Pro and Arg25Pro polymorphisms was different between patients and controls: Leu/Leu, Leu/Pro, Pro/Pro: 0.35, 0.50, 0.15 vs. 0.30, 0.24, 0.46 (p=0.001) and Arg/Arg, Arg/Pro, Pro/Pro: 0.79, 0.21, 0 vs. 0.87, 0.10, 0.03 (p=0.019). Similarly, haplotypes constructed with the combination of both polymorphisms were different among groups. There were no differences in CRD progression rate among genotypes. Codon 10 Leu allele was associated with the presence of clinical CVD in the ESRD patients (Leu/Leu, Leu/Pro, Pro/Pro: with CVD 0.49, 0.49,0.02 vs. without CVD 0.27, 0.51, 0.22 (p=0.01). Combined polymorphism haplotypes were also significantly different between ESRD patients with and without CVD. This association was independent from other risk factors. Conclusions: TGF-β1 polymorphisms are associated with ESRD, particularly in patients with associated clinical CVD, and could be useful as genetic markers of CRD and higher cardiovascular risk.