Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues.
Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues.
复制标题
感染肝组织中丙型肝炎病毒基因组的全面DNA甲基化分析。
DOI：
10.1038/srep10478
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发表时间：
2015-05-22
影响因子：
4.6
通讯作者：
Su YH
中科院分区：
文献类型：
--
作者：
Jain S;Chang TT;Chen S;Boldbaatar B;Clemens A;Lin SY;Yan R;Hu CT;Guo H;Block TM;Song W;Su YH
乙型肝炎病毒（HBV）是一种嗜肝病毒，可引起肝炎、肝硬化和肝细胞癌（HCC）。不同形式的 HBV DNA 的甲基化状态可能有助于深入了解 HBV 相关肝脏疾病（包括 HCC）的发病机制，但这尚不清楚。本研究的目的是获得受感染肝脏中 HBV DNA 中三个假定 CpG 岛的全面 DNA 甲基化谱，与肝病进展相关。首先使用亚硫酸氢盐 PCR 测序对一小组组织样本评估这些 CpG 岛的甲基化程度，然后使用定量亚硫酸氢盐特异性 PCR 和定量甲基化特异性 PCR 测定在较大样本量 (n = 116) 中进行分析。 HBV CpG岛3甲基化水平与肝癌发生显着相关。我们还首次获得了感染肝脏中 HBV 基因组 CpG 岛 2 中罕见的非 CpG 甲基化的证据。将 HBV 基因组的甲基化与三个已知的 HCC 相关宿主基因 APC、GSTP1 和 RASSF1A 进行比较，我们没有发现这两组之间存在显着相关性。
Hepatitis B virus (HBV) is a hepatotropic virus causing hepatitis, cirrhosis and hepatocellular carcinoma (HCC). The methylation status of the HBV DNA in its different forms can potentially provide insight into the pathogenesis of HBV-related liver diseases, including HCC, however this is unclear. The goal of this study is to obtain comprehensive DNA methylation profiles of the three putative CpG islands in the HBV DNA in infected livers, with respect to liver disease progression. The extent of methylation in these CpG islands was first assessed using bisulfite PCR sequencing with a small set of tissue samples, followed by analysis using both quantitative bisulfite-specific PCR and quantitative methylation-specific PCR assays in a larger sample size (n = 116). The level of HBV CpG island 3 methylation significantly correlated with hepatocarcinogenesis. We also obtained, for the first time, evidence of rare, non-CpG methylation in CpG island 2 of the HBV genome in infected liver. Comparing methylation of the HBV genome to three known HCC-associated host genes, APC, GSTP1, and RASSF1A, we did not identify a significant correlation between these two groups.