乙型肝炎病毒PreC/C及S基因抗原表位突变对慢性乙型肝炎患者HBeAg血清学状态的影响  

Effect of hepatitis B virus preC/C and S gene antigen epitope mutations on HBeAg serological status in patients with chronic hepatitis B

作　　者：李虎 彭明利[1] 陈敏[1] 任红[1] 胡鹏[1] Li Hu;Peng Mingli;Chen Min;Ren Hong;Hu Peng(Department of Infectious Diseases,Institute for Viral Hepatitis,the Key Laboratory of Molecular Biology for Infectious Diseases,Chinese Ministry of Education,the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China)

机构地区：[1]重庆医科大学病毒性肝炎研究所,感染性疾病分子生物学教育部重点实验室,重庆医科大学附属第二医院感染科,400010

出　　处：《中华肝脏病杂志》2020年第7期586-590,共5页Chinese Journal of Hepatology

基　　金：国家自然科学基金(81902068);十三五国家科技重大专项(2017ZX10202203-008)。

摘　　要：目的:探讨HBV PreC/C及S基因抗原表位的突变对慢性乙型肝炎患者HBeAg血清学状态的影响。方法:在横断面研究中,通过纳入35例未经抗病毒治疗慢性乙型肝炎患者,采用巢式PCR-TA克隆-测序方法筛选与HBeAg血清学状态相关的HBV PreC/C和S基因突变位点。然后在纵向研究中(60例)利用多元回归模型校正相关混杂因素,探讨HBV PreC/C及S基因抗原表位的突变与HBeAg状态之间的独立关系。结果:在横断面研究中,64.4%的PreC/C突变和68.2%的S突变发生在抗原表位区。有10个突变位点(PreC/C50、55、79、84、103、126、145、184和s110、s213)与HBeAg阴性状态相关( P < 0.05)。在纵向研究中校正了年龄、性别、HBV基因型、血清丙氨酸转氨酶水平和PreC W28*突变等混杂因素后,结果显示Tc细胞表位(PreC47-56、PreC117-125、s208-216)和Th细胞表位(PreC176-185)的突变是影响宿主HBeAg血清学状态的主要独立危险因素。 结论:HBV PreC/C区(PreC47-56、PreC117-125和PreC176-185)和S区(s208-216)表位的突变是影响宿主HBeAg状态的主要独立因素,提示这些抗原表位的突变可能参与HBeAg的血清学转换。Objective To explore the effect of HBV preC/C and S gene antigen epitope mutations on HBeAg serological status in patients with chronic hepatitis B.Methods Thirty-five cases with chronic hepatitis B without antiviral therapy were enrolled in this cross-sectional study.Nested PCR-TA cloning-sequencing method was used to screen HBV preC/C and S gene mutation sites related to HBeAg serological status.Then,in the longitudinal study(60 cases),the independent correlation between HBV preC/C and S gene antigen epitopes mutations and HBeAg status was explored by using multiple regression models to correct the correlated confounding factors.Results In this cross-sectional study,64.4%of preC/C and 68.2%of S mutations had occurred in the epitope region.There were ten mutation sites(PreC/C50,55,79,84,103,126,145,184 and s110,s213)correlated with HBeAg negative status(P<0.05).After adjusting for confounding factors such as age,gender,HBV genotype,serum alanine aminotransferase level and precw28*mutations in the longitudinal studies,the results showed that TC cell epitope(prec47-56,prec117-125,s208-216)and Th cell epitope(prec176-185)were the main independent risk factors affecting the host HBeAg serological status.Conclusion HBV preC/C region(PreC47-56,PreC117-125 and PreC176-185)and S region(s208-216)epitope mutations are the main independent factors affecting the host HBeAg status,suggesting that these epitope mutations may be involved in the HBeAg seroconversion.

关 键 词：肝炎 乙型 慢性 肝炎病毒 乙型 表位 突变 

分 类 号：R512.62[医药卫生—内科学]