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  • Title: [Effect of polymorphism of transforming growth factor beta1 gene on HBV-induced liver cirrhosis].
    Author: Yang ZX, Wang H, Gao CF, Xu LL, Zhao WJ.
    Journal: Zhonghua Yi Xue Za Zhi; 2005 Apr 20; 85(15):1021-6. PubMed ID: 16029542.
    Abstract:
    OBJECTIVE: To explore the effects of transforming growth factor beta1 (TGFbeta1) gene polymorphism on liver cirrhosis induced by HBV infection and on plasma concentration of TGFbeta1. METHODS: Peripheral blood samples were collected from 134 patients with HBV-induced liver cirrhosis, which were further classified into three groups (A, B and C groups) according to Child-Pugh classification and 92 healthy blood donors. The polymorphisms at position -988, -800, -509 and codon10, codon25, and codon263 of TGFbeta1 gene were determined by PCR-ARMS- and Lightcycler respectively, combined with sequence analysis. The concentrations of TGFbeta1 and collagen type IV were measured by ELISA, and the plasma concentrations of hyaluronan and N-terminal type III procollagen peptide were measured by RIA. ARLEQUIN Ver 2.0 software was used to analyze the linkage disequilibrium between -509C > T and codon10T > C polymorphisms. RESULTS: No polymorphism was found at positions -800, -988, codon25 and codon263. No significant difference for -509C > T polymorphism between the diseased and control groups was found, however, the frequencies of genotype TT and allele T at codon10 in the diseased group were 0.313 and 0.537 respectively, both significantly higher than those of the control group (0.916 and 0.440 respectively, both P < 0.05). In Child-Pugh C grade group the frequency of C allele at position -509 was 0.631, significantly higher than that of T allele (0.325), but there was no significant difference for codon10T > C polymorphism. The TGFbeta1 plasma concentration did not show any difference between the genotypes -509CC and TT in the control group, however, the TGFbeta1 plasma concentration was statistically lower in the those with TT genotype than in those with CC genotype in the diseased group. Linkage disequilibrium was found between -509C > T and codon10T > C polymorphisms and the major haplotypes were C-T and T-C, of which C-T frequency was significantly higher in the patients than in the control group. The plasma concentration of TGFbeta1 was significantly higher in the populations of haplotype C-T than in those of other haplotypes. CONCLUSION: No relationship is found between -509C > T polymorphism of TGFbeta1 and liver cirrhosis in Chinese populations, but the presence of C allele at position -509 may play an important role in the progression of liver cirrhosis and may influence plasma concentration of TGFbeta1 in liver cirrhosis patients. Codon10T > C polymorphism may play a significant role in development of liver cirrhosis, but has no correlation with plasma concentration of TGFbeta1 and progression of liver cirrhosis. The -509C > T and codon10T > C polymorphisms are in tight linkage disequilibrium, and the major haplotypes are C-T and T-C. The haplotype C-T influences plasma concentration of TGFbeta1 and is closely related to liver cirrhosis.
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