[Role of transforming growth factor beta-1 gene polymorphisms in the development of chronic allograft nephropathy in renal transplant recipients].

BACKGROUND: Chronic allograft nephropathy (CAN) is the main cause of graft loss after the first year of transplantation, and renal biopsies show a predominance of fibrotic lesions. Human transforming growth factor beta-1 (TGF-beta 1) is the principal profibrogenetic cytokine which has been recently implicated in the development of CAN. Seven TGF-beta 1 gene polymorphisms have been recently described and some of them have been related to the development of several diseases. AIM: To analyse the relationship between TGF-beta 1 gene polymorphisms and the development of CAN in a group of renal transplant patients with a long-term follow-up. METHODS: A restriction enzyme-based method for TGF-beta 1 genotyping was used to detect four TGF-beta 1 gene polymorphisms in codon 10, 25 and 5'-flanking region (-800 and -509 positions). A retrospective case-control study were performed on sixty renal transplant recipients with 8 years of post-transplant, 22 of them with CAN (cases) and 38 with normal graft function (controls). We studied 73 subjects to analyse the distribution of the genotypes in the area. RESULTS: The genotype frequencies were similar in the study and control group. The presence of chronic allograft nephropathy was statistically associated with the combination Pro/Pro10 TT509 polymorphism in the TGF-beta 1 gene, and these patients develop chronic rejection more quickly than the rest of the patients. Chronic allograft nephropathy was also associated with delta age recipient-donor, with older donors being a significant risk factor for chronic nephropathy. The logistic regression analysis confirmed the independent role of TT509 Pro/Pro10 TGF-beta 1 polymorphism with a Odd Ratio of 5.8 (1.14-29.7) in chronic nephropathy being the delta age recipient-donor a confounder factor but not an effect modifier. The rest of the TGF-beta 1 gene polymorphisms and the classic risk factors were not associated with the development of chronic allograft nephropathy. CONCLUSIONS: These data suggest a leading role for TGF-beta 1 gene polymorphisms (TT509 Pro/Pro10) in the development of chronic allograft nephropathy. The identification of this genetic predisposition to chronic allograft rejection could play a decisive role in the prevention of this common pathology.