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丙型肝炎病毒核心基因特征性突变与肝细胞癌发生的关系。

Characteristic mutations in hepatitis C virus core gene related to the occurrence of hepatocellular carcinoma.

机构信息

Unit of Disease Control Genome Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

出版信息

Cancer Sci. 2009 Dec;100(12):2465-8. doi: 10.1111/j.1349-7006.2009.01338.x.

Abstract

Chronic hepatitis C virus (HCV) infection often results in hepatocellular carcinoma (HCC). Previous studies have shown that there might be some characteristic mutations in the core region of HCV related to HCC. Thus, we downloaded and analyzed HCV genotype 1b core gene sequences from HCV databases online to identify them. Based on the information of the sequences, 63 from patients with HCC and 188 from non-HCC were enrolled into our analysis. Then, the nucleotides at each position were compared by chi(2)-test between the two groups, and 24 polymorphisms were found to be associated with HCC. Further analysis of these 24 polymorphisms by logistic regression indicated that eight were significantly related to the increased HCC risk: A028C, G209A, C219U/A, U264C, A271C/U, C378U/A, G435A/C, and G481A. Moreover, U303C/A was associated with the decreased HCC risk. These mutations could bring about four amino acid substitutions: K10Q, R70Q, M91L, and G161S. In conclusion, eight characteristic mutations in the HCV-1b core gene related to the occurrence of HCC were identified. The structural and functional alterations of core protein due to these mutations and the relationship with the occurrence of HCC need to be further studied.

摘要

慢性丙型肝炎病毒 (HCV) 感染常导致肝细胞癌 (HCC)。先前的研究表明,HCV 核心区可能存在一些与 HCC 相关的特征性突变。因此,我们从在线 HCV 数据库中下载并分析了 HCV 基因 1b 核心基因序列以识别这些突变。基于序列信息,我们将 63 例 HCC 患者和 188 例非 HCC 患者纳入分析。然后,通过卡方检验比较两组中每个位置的核苷酸,发现 24 个多态性与 HCC 相关。通过 logistic 回归对这 24 个多态性进一步分析表明,8 个与 HCC 风险增加显著相关:A028C、G209A、C219U/A、U264C、A271C/U、C378U/A、G435A/C 和 G481A。此外,U303C/A 与 HCC 风险降低相关。这些突变可能导致 4 个氨基酸取代:K10Q、R70Q、M91L 和 G161S。总之,鉴定出与 HCC 发生相关的 HCV-1b 核心基因中的 8 个特征性突变。这些突变导致核心蛋白的结构和功能改变以及与 HCC 发生的关系需要进一步研究。

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