Abstract
武佳欣,杨志清,张睿君,李雁笛,赵甜静,扆琳珠,冯永亮,丰淑英,汪波,王素萍.HBsAg阳性母亲HBV核心启动子突变与宫内传播的关系[J].Chinese journal of Epidemiology,2020,41(6):902-907
HBsAg阳性母亲HBV核心启动子突变与宫内传播的关系
Relationship between mutations of HBV basal core promoter region in HBsAg-positive mothers and intrauterine transmission
Received:February 24, 2020  
DOI:10.3760/cma.j.cn112338-20200224-00163
KeyWord: 乙型肝炎病毒宫内传播  核心启动子  HBs抗原  HBe抗原  A1762T/G1764A
English Key Word: Intrauterine transmission  Basal core promoter  HBsAg  HBeAg  A1762T/G1764A
FundProject:国家自然科学基金(81573212,81872677);传染病预防控制国家重点实验室自主研究课题(2017SKLID306,2018SKLID310)
Author NameAffiliationE-mail
Wu Jiaxin Department of Epidemiology, Shanxi Medical University, Taiyuan 030001, China  
Yang Zhiqing Department of Epidemiology, Shanxi Medical University, Taiyuan 030001, China  
Zhang Ruijun Department of Epidemiology, Shanxi Medical University, Taiyuan 030001, China  
Li Yandi Department of Epidemiology, Shanxi Medical University, Taiyuan 030001, China  
Zhao Tianjing Department of Epidemiology, Shanxi Medical University, Taiyuan 030001, China  
Yi Linzhu Department of Epidemiology, Shanxi Medical University, Taiyuan 030001, China  
Feng Yongliang Department of Epidemiology, Shanxi Medical University, Taiyuan 030001, China fengyongliang048@163.com 
Feng Shuying Department of Obstetrics and Gynaecology, the Third People Hospital of Taiyuan City, Taiyuan 030001, China  
Wang Bo Department of Obstetrics and Gynaecology, the Third People Hospital of Taiyuan City, Taiyuan 030001, China  
Wang Suping Department of Epidemiology, Shanxi Medical University, Taiyuan 030001, China spwang88@163.com 
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Abstract:
      目的 分析HBV为C基因型的HBsAg阳性母亲核心启动子(BCP)区突变与宫内传播的关系。方法 2011年6月至2013年7月太原市第三人民医院妇产科HBsAg阳性母亲及新生儿399对。收集一般人口学资料,采用荧光定量PCR和电化学发光法分别检测母婴血清HBV DNA及HBV血清学标志物。选择HBV DNA载量≥106 IU/ml的113例母亲为研究对象,其新生儿发生宫内传播的22例为宫内传播组,随机选取其中22例未发生宫内传播者作为对照组,母亲HBV DNA经提取、扩增、克隆、测序和序列编辑及剪接后与从NCBI下载的标准序列比对进行基因分型,最终选择C基因型的39例母亲进行突变分析。结果 HBV为C基因型(88.63%)的母亲共39例,其中宫内传播组19例,对照组20例。母亲A1762T/G1764A双突变率在两组差异显著(7.53% vs.27.72%,P<0.001)。非条件logistic回归分析显示A1762T/G1764A双突变可能是宫内传播的保护因素(aOR=0.065,95% CI:0.006~0.746,P=0.028)。母亲A1762T/G1764A双突变可能与新生儿HBeAg水平有关(P=0.050)。结论 HBV C基因型的HBsAg阳性母亲HBV DNA BCP区A1762T/G1764A双突变可能降低HBV宫内传播的风险。
English Abstract:
      Objective To analyze the relationship between maternal mutations in basal core promoter region of hepatitis B virus (HBV) genotype C and intrauterine transmission. Methods We collected information on general demographic characteristics and process of delivery among 399 pairs of consecutive HBsAg-positive mothers and their neonates, from the Third People’s Hospital of Taiyuan in Shanxi province, China. Fluorescence quantitative polymerase chain reaction (FQ-PCR) and Electro-chemiluminescence immuno-assay (ECLIA) kits were used to detect both maternal and neonatal HBV DNA and serological markers in the peripheral blood. From 113 mothers with HBV DNA load ≥106 IU/ml, we selected 22 mothers whose neonates were with intrauterine transmission and randomly selected the same number of mothers whose neonates were without intrauterine transmission, as controls. The whole-length HBV DNA were extracted, amplified, cloned, sequenced and genotyped. Finally, a total of 39 mothers with genotype C of HBV were selected for mutation analysis. Results Thirty-nine cases of genotype C (88.63%) were finally included in the study, with 19 cases in the intrauterine transmission group and 20 cases as controls. Rates of A1762T/G1764A double mutations were significantly different between the intrauterine transmission group and the control group (7.53% vs. 27.72%, P<0.001). Results from the multivariate analysis showed that the A1762T/G1764A double mutations had reduced the risk of intrauterine transmission (aOR=0.065, 95%CI: 0.006-0.746, P=0.028). Maternal A1762T/G1764A double mutations appeared to be possibly associated with neonatal HBeAg (P=0.050). Conclusion A1762T/G1764A double mutations of HBV DNA from the genotype C of those HBsAg-positive mothers could reduced the risk of HBV intrauterine transmission during pregnancy.
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