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  • Title: Transforming growth factor beta 1 gene variants increase transcription and are associated with liver cirrhosis in Chinese.
    Author: Wang H, Zhao YP, Gao CF, Ji Q, Gressner AM, Yang ZX, Weiskirchen R.
    Journal: Cytokine; 2008 Jul; 43(1):20-5. PubMed ID: 18547814.
    Abstract:
    BACKGROUND AND AIMS: Transforming growth factor beta1 (TGFbeta1) acts as an important profibrogenic cytokine in liver fibrogenesis. The aim of this study was to explore the association between TGFbeta1 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 TGFbeta1 gene were genotyped by ARMS-PCR or LightCycler. Enzyme immunoassay was used for TGFbeta1 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 codon10 were elevated in patients at severe Child-Pugh grade. Elevated concentrations of TGFbeta1 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.
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