Nucleotide change of codon 182 in the surface gene of hepatitis B virus genotype C leading to truncated surface protein is associated with progression of liver diseases
Nucleotide change of codon 182 in the surface gene of hepatitis B virus genotype C leading to truncated surface protein is associated with progression of liver diseases
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DOI：
10.1016/j.jhep.2011.06.028
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发表时间：
2012-01-01
影响因子：
25.7
通讯作者：
Kim, Bum-Joon
中科院分区：
文献类型：
--
作者：
Lee, Seoung-Ae;Kim, Kijeong;Kim, Bum-Joon
背景和目的：乙型肝炎病毒（HBV）C 基因型感染与肝细胞癌（HCC）的进展相关。据报道，HBV 表面 (S) 基因的特定突变会导致 HCC 的发生。在这项研究中，研究了导致 C 基因型 S 基因密码子 182 过早终止的新型核苷酸变化 (sW182*) 与 HCC 的发生有关。方法：开发了一种能够快速可靠地检测 sW182* 的多探针实时 PCR，并将其应用于来自患有多种慢性肝病的韩国患者的 292 个 DNA 样本。结果：在韩国的 73 名患者中检测到了 sW182*。阳性扩增 275 例（26.5%）。进展型疾病（HCC 和肝硬化）患者的患病率显着高于病情较轻的患者（慢性肝炎和携带者）[31.8%（56/176 例患者）vs. 17.2%（17/99 例患者）； p = 0.010]。此外，一项使用稳定表达带有 sW182* 的 S 蛋白的细胞系的体外研究也有力地支持了其与 HCC 的关系。结论：在本研究中，我们通过分子流行病学和体外研究证明 HBV 的 sW182* 可以对肝病的进展做出重要贡献。 (C) 2011 年欧洲肝脏研究协会。由 Elsevier B.V 出版。保留所有权利。
Background & Aims: Hepatitis B virus (HBV) genotype C infection is associated with progression of hepatocellular carcinoma (HCC). Specific mutations of the HBV surface (S) gene have been reported to contribute to the development of HCC. In this study, novel nucleotide changes (sW182*) that result in a premature stop at codon 182 in the S gene of genotype C are investigated with regards to the development of HCC.Methods: A multi-probe real time PCR that enables rapid and reliable detection of sW182* was developed and applied to 292 DNA samples from Korean patients with diverse chronic liver diseases.Results: sW182* was detected in a total of 73 patients out of the 275 with positive amplification (26.5%). Its prevalence was significantly higher in patients with progressive forms of the disease (HCC and liver cirrhosis) than in patients with less severe forms of the disease (chronic hepatitis and carrier) [31.8% (56/176 patients) vs. 17.2% (17/99 patients); p = 0.010]. In addition, an in vitro study using cell lines stable expressing the S protein with sW182* also strongly supported its relationship with HCC.Conclusions: In the present study, we demonstrate that the sW182* of HBV could provide an important contribution to the progression of liver diseases, through molecular epidemiologic and in vitro studies. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.