Falleti Edmondo, Fabris Carlo, Toniutto Pierluigi, Fontanini Elisabetta, Cussigh Annarosa, Bitetto Davide, Fornasiere Ezio, Avellini Claudio, Minisini Rosalba, Pirisi Mario
Laboratory Medicine, DPMSC, University of Udine, Italy.
Cytokine. 2008 Nov;44(2):256-61. doi: 10.1016/j.cyto.2008.08.008. Epub 2008 Sep 21.
This study aimed to verify whether specific single nucleotide polymorphisms (SNPs) of the transforming growth factor-beta1 (TGF-beta1) may predispose to end-stage liver disease and/or hepatocellular carcinoma (HCC). One hundred eighty-eight consecutive patients transplanted for liver cirrhosis (HBV N=21, HCV N=68, alcoholic N=55 and others N=23) and a control group of 140 healthy blood donors were investigated. Four SNPs were studied by restriction fragment length assays: -800G>A, -509C>T, Leu10Pro and Arg25Pro. Patients were found to possess the -509T/ * (TT 53/188, CT 85/188, CC 50/188 vs TT 22/140, CT 61/140, CC 57/140; p<0.002) and Arg25Pro C/ * genotypes (CC 1/188, CG 31/188, GG 156/188 vs CC 0/140, CG 13/140, GG 127/140; p<0.05) more frequently than controls. Patients with cirrhosis complicated by HCC possessed more frequently the Leu10Pro T/ * genotype than patients without HCC (TT 20/54, CT 26/54, CC 8/54 vs TT 31/134, CT 69/134, CC 34/134; p<0.05). The analysis of molecular variance detected significant genotypic differentiations between controls and cirrhotics but not between cirrhotics with or without HCC. In conclusion, TGF-beta1 SNPs probably facilitate the development of liver cirrhosis, while they seem to have a limited role in predicting the occurrence of HCC.
本研究旨在验证转化生长因子-β1（TGF-β1）的特定单核苷酸多态性（SNP）是否易导致终末期肝病和/或肝细胞癌（HCC）。对188例因肝硬化接受移植的连续患者（乙肝病毒感染患者21例、丙肝病毒感染患者68例、酒精性肝硬化患者55例及其他病因患者23例）和140名健康献血者组成的对照组进行了调查。通过限制性片段长度分析研究了4个SNP：-800G>A、-509C>T、Leu10Pro和Arg25Pro。发现患者比对照组更频繁地出现-509T/*（TT 53/188、CT 85/188、CC 50/188，对照组为TT 22/140、CT 61/140、CC 57/140；p<0.002）和Arg25Pro C/*基因型（CC 1/188、CG 31/188、GG 156/188，对照组为CC 0/140、CG 13/140、GG 127/140；p<0.05）。与无HCC的患者相比，合并HCC的肝硬化患者更频繁地出现Leu10Pro T/*基因型（TT 20/54、CT 26/54、CC 8/54，无HCC患者为TT 31/134、CT 69/134、CC 34/134；p<0.05）。分子方差分析检测到对照组与肝硬化患者之间存在显著的基因型差异，但有或无HCC的肝硬化患者之间无显著差异。总之，TGF-β1 SNP可能促进肝硬化的发展，而它们在预测HCC发生方面似乎作用有限。
