乙肝病毒感染者HBV基因突变与疾病进展的关系研究  

Study on the relationship between HBV gene mutation and disease progression in patients with hepatitis B virus infection

作　　者：韩素雅 张爽[1] 唐林 苏秋东[1] 王富珍[2] 王锋[1] 郑徽[2] 邱丰[1] 李红艺[3] 王宇[3] 沈立萍[1] Han Suya;Zhang Shuang;Tang Lin;Su Qudong;Wang Fuzhen;Wang Feng;Zheng Hui;Qiu Feng;Li Hongyi;Wang Yu;Shen Liping(NHC Key Laboratory of Medical Viruses and Viral Diseases,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China;Department of National Immunization Program,Chinese Center for Disease Control and Prevention,Beijing 100050,China;Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]中国疾病预防控制中心病毒病预防控制所国家卫生健康委医学病毒和病毒病重点实验室,北京102206 [2]中国疾病预防控制中心免疫规划中心,北京100050 [3]首都医科大学附属北京友谊医院,北京100050

出　　处：《中华实验和临床病毒学杂志》2024年第1期21-28,共8页Chinese Journal of Experimental and Clinical Virology

基　　金：国家科技重大专项(2017ZX10105015-001-002)。

摘　　要：目的分析乙型肝炎病毒(HBV)感染者在不同疾病进展阶段的HBV全基因序列以及关键位点突变情况, 了解HBV基因特征与疾病进展的关系。方法收集无症状HBV携带者、慢性乙型肝炎患者、肝硬化患者以及原发性肝细胞癌患者四种乙肝感染者的血清样本和基本信息, 采用巢式PCR法扩增样本获得HBV全基因序列, 构建系统发育树确定样本基因型别, 结合各型别参考序列分析样本的基因突变情况。结果成功扩增256份样本, 包括无症状HBV携带组68例、CHB组118例、LC组15例和HCC组55例, 检出B、C、D、I和C/D重组型5种基因型。结果发现有56个核苷酸位点突变率在四组之间有统计学差异(P<0.05);除发现C105T、A1762T/G1764A、G1899A等一些既往报导的关键位点突变以外, 还发现HCC组的T791A、C1485T、C1023T等位点突变率显著高于其他组;无症状HBV携带组的T2150G、T2151C显著高于其他组;发生缺失突变的序列共计24条, 分布在前S区和前C区, HCC组的缺失突变率显著高于其他组。结论本研究发现T791A、C1485T、C1023T等核苷酸位点置换突变可能与HBV疾病进展密切相关, HCC患者较非HCC患者更容易发生HBV基因缺失, 研究结果为了解病毒变异与HBV感染相关疾病进展的关系提供参考。Objective To analyze the whole genome sequence and key site mutations of hepatitis B virus(HBV)in patients with different stages of disease progression,and to understand the relationship between HBV genetic characteristics and disease progression.Methods Serum samples and basic information of hepatitis B patients with asymptomatic HBV carrier,chronic hepatitis B patients,cirrhosis patients and primary hepatocellular carcinoma patients were collected.Nested PCR was used to amplify the samples to obtain HBV whole gene sequences.Phylogenetic trees were constructed to determine the genotype of the samples,and gene mutations of the samples were analyzed combined with reference sequences of each type.Results A total of 256 samples were successfully amplified,including 68 asymptomatic HBV carrier patients,118 CHB patients,15 LC patients and 55 HCC patients,and five genotypes(B,C,D,I and C/D)were detected.The result of comparative analysis showed that the mutation rate of 56 nucleotide sites was significantly different among the four groups(P<0.05).In addition to the discovery of C105T,A1762T/G1764A and G1899A and other previously reported key site mutations,the mutation rates of T53A,C1485T and C1628T in newly diagnosed HCC group were significantly higher than those in other groups,and the mutation rates of T2150G and T2151C in asymptomatic HBV infection group were significantly higher than those in other groups.A total of 26 sequences were deleted,mainly distributed in the pre-C and pre-S regions.The deletion mutation rate in the HCC group was significantly higher than that in the other groups.Conclusions The data of this study indicate that some nucleotide substitution mutations and deletion mutations may be closely related to the occurrence and development of HBV-related diseases,and HCC patients are more likely to have gene mutations than non-HCC patients.These result provide a reference for understanding the relationship between viral mutation and the progression of HBV infection-related diseases.

关 键 词：乙型肝炎病毒 基因突变 基因型 

分 类 号：R512.62[医药卫生—内科学]