慢性乙型肝炎、乙型肝炎肝硬化及原发性肝部患者HBV-X基因突变分析

发布时间：2018-08-10 17:39

【摘要】：背景：乙型肝炎病毒X基因（Hepatitis B virus X gene，HBV-X基因）在慢性乙型肝炎（chronic hepatitis B, CHB）发展为肝硬化（livercirrhosis，LC）及原发性肝癌（primary liver cancer, PLC）的过程中发挥重要作用。在HBV-X基因整合至宿主基因组的过程中，常发生X基因序列的突变甚至断裂不全，从而影响HBV的复制，与肝癌的发生密切相关。目的：研究慢性HBV感染患者，如慢性乙型肝炎、乙型肝炎肝硬化、原发性肝癌患者血清中HBV-X基因序列的突变与肝癌发生的关系。方法：收集2011-2013年间于重庆医科大学附属第二医院就诊的慢性HBV感染患者血清共89例，从血清中提取HBV-DNA,扩增全长HBV-X基因序列，经测序后，与已知的HBV-X基因相应序列比较，从而分析该患者体内HBV-X基因的变异形式及变异位点，并用卡方检验、单因素方差分析处理数据，NCBI的genotype工具测定基因型。结果：所有的患者均属于B/C基因型，HBeAg阳性患者中B基因型占46.2%，Ｃ基因型占53.8%，HBeAg阴性患性中B基因型占81.2%，Ｃ基因型占18.8%（P=0.001）。在原发性肝癌组中，启动子（basalcore promoter，BCP）区的突变显著高于CHB、LC(69.2%vs34.4%和61.3%，P0.05)，且nt1821位点存在明显的T碱基的缺失（88.5%vs53.1%和71%，P=0.014）。在慢性乙型肝炎、肝硬化中，，C基因型BCP的双突变率显著高于B基因型（61.5%vs15.8%，P=0.007；83.3%vs47.4%，P=0.045），HBV-DNA低病毒载量（≤10^6copies/ml）中BCP的突变率较高病毒载量（10^6copies/ml）更显著（81.3%vs47.9%，P=0.015）。结论：BCP区的双突变及nt1821位点的缺失可能与原发性肝癌的发生密切相关。
[Abstract]:BACKGROUND: Hepatitis B virus X gene (HBV-X gene) plays an important role in the development of chronic hepatitis B (CHB) into liver cirrhosis (LC) and primary liver cancer (PLC). The mutation of the sequence is even incomplete, which affects the replication of HBV, which is closely related to the occurrence of liver cancer.
Objective: To study the relationship between the mutation of HBV-X gene sequence and hepatocarcinogenesis in serum of patients with chronic hepatitis B, hepatitis B cirrhosis and primary hepatocellular carcinoma.
Methods: A total of 89 patients with chronic HBV infection who were admitted to the Second Affiliated Hospital of Chongqing Medical University from 2011 to 2013 were collected. HBV-DNA was extracted from the serum and the full-length HBV-X gene sequence was amplified. After sequencing, the HBV-X gene was compared with the corresponding sequence of known HBV-X gene. The data were processed by chi square test, single factor analysis of variance, and the genotype of NCBI was measured by the genotype tool.
Results: All patients belonged to B/C genotype. The B genotype accounted for 46.2% in HBeAg positive patients, 53.8% in C genotype, 81.2% in HBeAg negative patients, and 18.8% in C genotype (P = 0.001). The mutation in the promoter (BCP) region was significantly higher than that in CHB, LC (69.2% vs 34.4% and 61.3%, P 0.05), and nt18.2% in HCC negative patients. In chronic hepatitis B and cirrhosis, the double mutation rate of BC P in genotype C was significantly higher than that in genotype B (61.5% vs 15.8%, P = 0.007, 83.3% vs 47.4%, P = 0.045), and the mutation rate of BC P in low HBV-DNA viral load (< 10 ^ 6 copies / ml) was more significant than that in high viral load (10 ^ 6 copies / ml). (81.3%vs47.9%, P=0.015).
Conclusion: The double mutation in BCP region and the deletion of nt1821 locus may be closely related to the occurrence of primary hepatocellular carcinoma.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62;R575.2

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