Transforming growth factor β1 gene variants increase transcription and are associated with liver cirrhosis in Chinese

Background and Aims: Transforming growth factor beta 1 (TGF beta 1) acts as an important profibrogenic cytokine in liver fibrogenesis. The aim of this study was to explore the association between TGF beta 1 gene polymorphisms and liver cirrhosis. Methods: Totally 118 Chinese suffering from liver cirrhosis induced by HBV infection and 104 healthy controls were recruited. The polymorphisms at positions -988, -800, -509 and codon10, codon25, codon263 of the TGF beta 1 gene were genotyped by ARMS-PCR or LightCycler. Enzyme immunoassay was used for TGF beta 1 measurement. The promoter activities and DNA-binding capacities containing -509C>T were analyzed by reporter gene and EMSA. Results: The allele frequencies of CAT -509 and of T at codon 10 were elevated in patients at severe Child-Pugh grade. Elevated concentrations of TGF beta 1 were observed in patients, especially in those with -509CC/CT and codon10 TT/TC. Flanking sequences containing -509C showed higher promoter activities than -509T. EMSA showed one nucleotide change at -509C>T influenced nuclear protein binding to the putative binding site. Conclusions: The C allele at -509 and the T allele at codon10 could play important roles in progression of liver cirrhosis. The C allele at -509 mediates higher transcriptional activity than the T allele providing a potential explanation for the clinical findings. (C) 2008 Elsevier Ltd. All rights reserved.