乙型肝炎病毒变异在母婴传播中的初步研究  

Hepatitis B virus mutations during mother-to-children transmission:apreliminary study

作　　者：谢震宇[1] 傅益飞 张爱华[1] 浦蕊 丁一波[2] 孙乔[1] 曹广文[2] 

机构地区：[1]上海市浦东新区疾病预防控制中心,上海200136 [2]第二军医大学热带医学与公共卫生学系流行病学教研室,上海200433

出　　处：《第二军医大学学报》2015年第7期715-721,共7页Academic Journal of Second Military Medical University

基　　金：上海市浦东新区卫生系统优秀青年医学人才培养计划(PWRq2011-31)~~

摘　　要：目的探索肝细胞癌(HCC)相关乙肝病毒(HBV)变异在母婴传播和婴儿慢性感染中的变化规律,为肝细胞癌的防控提供理论依据。方法将413名HBV表面抗原(HBsAg)阳性产妇及其新生儿纳入本研究。应用定量PCR检测产妇外周血和新生儿脐带血HBV DNA,应用巢式PCR和克隆测序方法测定前S区和核心启动子区的HCC相关HBV变异。新生儿出生后均经标准HBV免疫,7个月后对104名婴儿HBV感染情况进行随访,对外周血HBV DNA阳性婴儿测定HCC相关HBV变异发生情况。结果在413名新生儿中,41名(9.9%)HBV DNA水平≥103 copies/mL。随访到的104名婴儿中,4名(占3.8%)HBV DNA≥103 copies/mL。与未发生HBV跨胎盘传播的产妇相比,发生HBV跨胎盘传播者外周血HBV核心启动子变异没有增加,但在C2基因亚型的前S区中,T2898G/C、C3000T、C3116T、T31C和T52C变异增加HBV跨胎盘传播的风险(P<0.05)。HBV基因组中前S区和核心启动子区的HCC相关变异的频率在产妇外周血和新生儿脐带血中无明显差别,但是在母婴传播的7个月龄HBV DNA阳性婴儿中,检测出极少数量。结论 HBV C2基因亚型的前S区某些变异可能影响HBV跨胎盘传播,但是具有HCC相关HBV变异的准种没有造成婴儿慢性感染的优势,促进HBV致癌的变异体是在漫长的慢性感染过程中逐渐被选择出来的。Objective To explore the mutations of hepatocellular carcinoma（HCC）-related hepatitis B virus（HBV）during mother-to-child transmission,so as to provide theoretic evidence for prophylaxis of HCC from the very beginning.Methods A total of 413 HBsAg-positive mothers and their newborns were enrolled in this study.Serum HBV DNA levels in maternal peripheral blood and cord blood of the newborns were measured using real-time quantitative PCR.Nested PCR together with cloning and sequencing methods were applied to examine the HCC-related HBV mutations in the preS and basal core promoter regions of HBV genome.All the newborns received standard HBV vaccination.Of the 413 newborns,104were successfully followed-up 7 months after birth,and the HBV mutations were examined if their circulating HBV DNA was detectable.Results Of the 413 newborns,41（9.9%）had HBV DNA level103 copies/mL in their cord blood.Four（3.8%）of the 104 newborns who were successfully followed up had circulating HBV DNA level103 copies/mL 7months after birth.Compared to mothers without HBV trans-placental transmission,those with HBV trans-placental transmission had no increase in HBV mutations in the basal core promoter region.However,the viral mutations containing T2898G/C,C3000 T,C3116T,T31 C,and T52 Cin the preS region of HBV subgenotype C2 significantly increased the risk of HBV trans-placental transmission（P〈0.05）.The frequencies of the HCC-related mutations in the preS and basal core promoter regions of HBV genome were not significantly different between maternal peripheral blood and the cord blood of the newborns.Importantly,the HCC-related mutations were rarely found in the HBV-positive infants at 7months after birth.Conclusion The HBV mutations in the preS region of HBV subgenotype C2 may affect the trans-placental transmission of HBV.However,the quasispecies of HCC-related HBV mutants have no advantage in causing chronic HBV infection in infants.The HBV mutants which can promote HCC are selected during the long term chronic infect

关 键 词：乙型肝炎病毒 肝细胞癌 变异(遗传学) 垂直疾病传播 

分 类 号：R512.62[医药卫生—内科学]