隐匿性乙型肝炎病毒复制相关基因甲基化水平的研究  

Study on methylation level of replication related genes of occult hepatitis B virus

作　　者：张美林 王瑞涛[1] 王珊[1] 哈丽米热·买买提 付薪静 周丽君[1] ZHANG Meilin;WANG Ruitao;WANG Shan;HA Limire Maimaiti;FU Xinjing;ZHOU Lijun(Urunmi Blood Center,Ururmji 8300U,China.)

机构地区：[1]乌鲁木齐市血液中心,新疆乌鲁木齐830011

出　　处：《中国输血杂志》2022年第2期138-144,共7页Chinese Journal of Blood Transfusion

基　　金：乌鲁木齐市卫健委科技计划项目(201826)。

摘　　要：目的研究隐匿性乙型肝炎病毒甲基化及复制相关基因的水平,探讨隐匿性乙型肝炎病毒甲基化水平对复制相关基因的影响。方法对照组(健康对照)、隐匿性乙型肝炎组(隐匿性HBV组)、乙型肝炎组(HBV组)各3例进行Illumina甲基化850k芯片检测,对其进行了差异分析、GO分析、KEGG分析,筛选出甲基化及病毒复制相关基因DNMT1、DNMT2及DNMT3a、ZHX2进行RT-PCR检测。结果隐匿性HBV组、HBV组甲基化程度较对照组明显升高;差异分析显示隐匿性HBV组同对照组相比有1 050个差异甲基化位点甲基化程度大于非甲基化程度,有1 340个差异甲基化位点甲基化程度小于非甲基化程度;HBV组有1 008个差异甲基化位点甲基化程度大于非甲基化程度,有1 242个差异甲基化位点甲基化程度小于非甲基化程度;GO分析显示,同对照组相比隐匿性HBV组、HBV组,差异基因表达同生物过程(BP)中、细胞组成(CC)中、分子功能(MF)中的许多合成代谢等过程显著相关;对照组同隐匿性HBV组KEGG通路富集分析发现,差异基因主要参与了粘连连接、基底细胞癌、子宫内膜癌、EB病毒感染、肝细胞癌等信号通路;隐匿性HBV组和HBV组KEGG通路富集分析发现,差异基因主要参与了AMPK信号通路、细胞周期、子宫内膜癌、丙型肝炎、肝细胞癌等信号通路;DNMT1、DNMT3a在隐匿性HBV组和HBV组中较对照组中明显升高;ZHX2在隐匿性HBV组和HBV组中较对照组中明显降低。结论隐匿性HBV组和HBV组甲基化水平明显升高,ZHX2在隐匿性HBV组和HBV组明显降低。高甲基化抑制了ZHX2的表达,改变了乙型肝炎病毒的复制。乙型肝炎病毒DNA甲基化为乙型肝炎病毒的复制机制提供理论依据和乙型肝炎病毒的治疗提供新思路、新方法。Objective To study the level of occult hepatitis B virus methylation and replication related genes, and to explore the effect of the former on the latter. Methods The cases in control group(healthy control, n=3), occult hepatitis B group(occult HBV group, n=3) and hepatitis B group(HBV group, n=3) were detected by Illumina methylation 850 k chip. The difference analysis, GO analysis and KEGG analysis were carried out. The methylation and virus replication related genes DNMT1, DNMT2, Dnmt3a and ZHX2 were screened for RT-PCR. Results The methylation level of occult HBV group and HBV group was significantly higher than that of the control group. Difference analysis showed that there were 1 050 differential methylation sites in occult HBV group with the methylation level greater than non-methylation level, and 1 340 differential methylation sites as the opposite compared with the control group. In HBV group, there were 1 008 differential methylation sites with methylation level greater than non-methylation level, and 1 242 differential methylation sites as the opposite. Go analysis showed that compared with the control group, the differential gene expression in occult HBV group and HBV group was significantly related to many anabolic processes in biological process(BP), cell composition(CC) and molecular function(MF).The enrichment analysis of KEGG pathway between the control group and the occult HBV group showed that the differential genes were mainly involved in adhesion junction, basal cell carcinoma, endometrial carcinoma, EB virus infection, hepatocellular carcinoma and other signal pathways. The enrichment analysis of KEGG pathway in occult HBV group and HBV group showed that the differential genes were mainly involved in AMPK signal pathway, cell cycle, endometrial cancer, hepatitis C, hepatocellular carcinoma and other signal pathways. DNMT1 and DNMT3a in occult HBV group and HBV group were significantly higher while ZHX2 was significantly lower than those in control group. Conclusion The methylation level of

关 键 词：隐匿性乙型肝炎 甲基化 差异基因表达 

分 类 号：R457.11[医药卫生—治疗学] R512.62[医药卫生—临床医学]