文章摘要
王婷,王丹丹,陈文鑫,晋聪,李雁笛,扆琳珠,丰淑英,汪波,冯永亮,王素萍.HBsAg阳性母亲C基因型HBV DNA CpG岛分布特点和宫内传播的关系[J].中华流行病学杂志,2022,43(5):728-733
HBsAg阳性母亲C基因型HBV DNA CpG岛分布特点和宫内传播的关系
Distributive characteristics of HBV DNA CpG islands in HBsAg positive mothers and its relationship with intrauterine transmission
收稿日期:2021-10-10  出版日期:2022-05-13
DOI:10.3760/cma.j.cn112338-20211010-00779
中文关键词: 乙型肝炎病毒;C基因型;CpG岛;宫内传播
英文关键词: Hepatitis B virus;Genotype C;CpG islands;Intrauterine transmission
基金项目:国家自然科学基金(81872677,81573212)
作者单位E-mail
王婷 山西医科大学公共卫生学院流行病学教研室/临床流行病学与循证医学中心, 太原 030001  
王丹丹 山西医科大学公共卫生学院流行病学教研室/临床流行病学与循证医学中心, 太原 030001  
陈文鑫 山西医科大学公共卫生学院流行病学教研室/临床流行病学与循证医学中心, 太原 030001  
晋聪 山西医科大学公共卫生学院流行病学教研室/临床流行病学与循证医学中心, 太原 030001  
李雁笛 山西医科大学公共卫生学院流行病学教研室/临床流行病学与循证医学中心, 太原 030001  
扆琳珠 山西医科大学公共卫生学院流行病学教研室/临床流行病学与循证医学中心, 太原 030001  
丰淑英 太原市第三人民医院妇产科, 太原 030001  
汪波 太原市第三人民医院妇产科, 太原 030001  
冯永亮 山西医科大学公共卫生学院流行病学教研室/临床流行病学与循证医学中心, 太原 030001  
王素萍 山西医科大学公共卫生学院流行病学教研室/临床流行病学与循证医学中心, 太原 030001 supingwang@sxmu.edu.cn 
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中文摘要:
      目的 探讨HBsAg阳性母亲C基因型HBV DNA CpG岛的类型、长度、CG位点等的分布特点及其与HBV宫内传播的关系,为HBV宫内传播机制研究提供新视角。方法 连续收集2011年6月至2013年7月太原市第三人民医院妇产科住院分娩的HBsAg阳性母亲及其新生儿,通过面对面问卷调查及电子病历收集流行病学资料,采用电化学发光法和荧光定量PCR分别检测母亲及新生儿HBV血清学标志物及血清HBV DNA。以新生儿出生24 h内乙型肝炎(乙肝)疫苗/乙肝免疫球蛋白注射前股静脉血HBsAg和/或HBV DNA阳性判定为HBV宫内传播。将HBV宫内传播者中HBV DNA载量≥106 IU/ml(满足克隆测序要求)的22例母亲及其新生儿作为宫内传播组,从未发生宫内传播者中随机选取HBV DNA载量≥106 IU/ml的22例作为对照组,以HBV DNA测序分型结果为C基因型的39例母亲进行HBV DNA CpG岛分布预测等分析。结果 39例HBV C基因型的母亲中,宫内传播组19例,对照组20例。39例C基因型者HBV DNA均含有传统CpG岛Ⅱ、岛Ⅲ,而对照组中有传统CpG岛Ⅰ以及新型CpG岛Ⅳ、岛Ⅴ;HBV宫内传播组和对照组母亲携带的HBV DNA CpG岛Ⅱ、岛Ⅲ长度和CpG岛Ⅱ CG位点个数分布不同,差异有统计学意义(P<0.05),HBV宫内传播组中CpG岛Ⅱ长度≥518 bp且其CG位点个数≥40个(11/19)的比例明显高于对照组(2/20),差异有统计学意义(P<0.05);位于X基因启动子区的CpG岛Ⅱ长度和CG位点个数大于对照组,差异有统计学意义(P<0.05)。HBV宫内传播组中大部分母亲(12/19)携带的HBV DNA CpG岛Ⅱ完全覆盖了Xp区,明显多于对照组(5/20),且其HBV DNA Xp区CG位点个数大于对照组,差异有统计学意义(P<0.05)。结论 HBsAg阳性母亲C基因型HBV DNA CpG岛分布与宫内传播有关,CpG岛Ⅱ长度长、CG位点个数多可能会增加HBV宫内传播的发生风险。
英文摘要:
      Objective To investigate the type, length, and CG loci of HBV DNA CpG islands in HBsAg positive maternal C genotype and its relationship with intrauterine HBV transmission, so as to provide a new perspective for the study of intrauterine transmission of HBV. Methods From June 2011 to July 2013, HBsAg-positive mothers and their newborns who delivered in the obstetrics and gynecology department of the Third People's Hospital of Taiyuan were collected. Epidemiological data were collected through face-to-face questionnaires and electronic medical records. Serum HBV markers and serum HBV DNA were detected by electrochemiluminescence and quantitative fluorescence PCR, respectively. Intrauterine transmission of HBV was determined by positive HBsAg and/or HBV DNA in femoral venous blood before injection of HBV vaccine/Hepatitis B immunoglobulin within 24 h of birth. A total of 22 mothers and their newborns with HBV DNA load ≥106 IU/ml in intrauterine transmission were selected as the intrauterine transmission group, and 22 mothers with HBV DNA load ≥106 IU/ml without intrauterine transmission were chosen as the control group by random seed method. The distribution prediction of CpG islands of HBV DNA in 39 mothers with genotype C by HBV DNA sequencing was analyzed. Results Among 39 mothers with HBV C genotype, 19 were in the intrauterine transmission group, and 20 were in the control group. The HBV DNA of 39 patients with genotype C traditional CpG island Ⅱ and Ⅲ, while the control group had traditional CpG island Ⅰ and novel CpG island Ⅳ and Ⅴ. The length of CpG island Ⅱ and Ⅲ and the number of CG loci of CpG island Ⅱ in the intrauterine transmission group differed from those in the control group (P<0.05). The CpG island Ⅱ length ≥518 bp and the number of CG loci ≥40 in the intrauterine transmission group (11/19) were significantly higher than those in the control group (2/20) (P<0.05). The length of CpG island Ⅱ and the number of CG loci in the X gene promoter region (Xp region) were higher than those in the control group (P<0.05). In the HBV intrauterine transmission group, most of maternal (12/19) HBV DNA CpG island Ⅱ completely covered the Xp region, which was significantly higher than that in the control group (5/20), and the number of HBV DNA Xp region CG loci was higher than that in the control group (P<0.05). Conclusion The distribution of maternal C genotype HBV DNA CpG islands is related to intrauterine transmission. The length of CpG island Ⅱ and the number of CG sites may increase the risk of intrauterine transmission of HBV.
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