Transforming growth factor-beta receptor 2 gene polymorphisms are associated with end-stage renal disease

ABSTRACT

BACKGROUND: Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine involved in immune disorders, cancer, asthma, lung fibrosis, and chronic kidney disease, and its signal pathways are considered crucial mediators of a variety of cellular processes. In addition, several recent studies have reported that TGF-beta receptor (TGF-betaR) gene polymorphism is associated with chronic kidney disease. However, the association between end-stage renal disease (ESRD) and the TGF-beta gene polymorphism has not been sufficiently investigated. In this study, we hypothesized that polymorphisms of the TGF-beta ligands or their receptors may be related to ESRD. METHODS: We assessed the relationship between four single-nucleotide polymorphisms (SNPs) in the TGF-betaR2 and TGF-beta2 genes and ESRD, in 312 patients with ESRD and 258 controls. RESULTS: Compared with the control participants, the frequencies of the TGF-betaR2 (rs764522*C) and TGF-betaR2 (rs3087465*G) alleles were significantly higher in the patients with ESRD. Genotyping analysis demonstrated that two SNPs in TGF-betaR2 of the four SNPs included in the study were significantly associated with ESRD in the codominant 1 [rs764522, odds ratio (OR)=1.65; rs3087465, OR=1.63], dominant (rs764522, OR=1.63; rs3087465, OR=1.57), and log-additive (rs764522, OR=1.54; rs3087465, OR=1.39) models after adjusting for age and sex. CONCLUSION: We suggest that TGF-betaR2 polymorphisms (rs764522 and rs3087465) increase the risk of development of ESRD.