Wang T, Wang D D, Chen W X, Jin C, Li Y D, Yi L Z, Feng S Y, Wang B, Feng Y L, Wang S P
Department of Epidemiology/Center of Clinical Epidemiology and Evidence-Based Medicine, Shanxi Medical University, Taiyuan 030001, China.
Department of Obstetrics and Gynaecology, the Third People Hospital of Taiyuan City, Taiyuan 030001, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2022 May 10;43(5):728-733. doi: 10.3760/cma.j.cn112338-20211010-00779.
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. 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 ≥10 IU/ml in intrauterine transmission were selected as the intrauterine transmission group, and 22 mothers with HBV DNA load ≥10 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. 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 (<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) (<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 (<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 (<0.05). 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.
探讨HBsAg阳性母亲C基因型HBV DNA CpG岛的类型、长度及CG位点，及其与HBV宫内传播的关系，为HBV宫内传播的研究提供新视角。收集2011年6月至2013年7月在太原市第三人民医院妇产科分娩的HBsAg阳性母亲及其新生儿。通过面对面问卷调查和电子病历收集流行病学资料。分别采用电化学发光法和荧光定量PCR法检测血清HBV标志物和血清HBV DNA。根据出生后24 h内注射HBV疫苗/乙肝免疫球蛋白前股静脉血中HBsAg和/或HBV DNA阳性确定HBV宫内传播。选取宫内传播组22例母亲及其新生儿（宫内HBV DNA载量≥10 IU/ml），采用随机数字表法选取22例无宫内传播且HBV DNA载量≥10 IU/ml的母亲作为对照组。通过HBV DNA测序分析39例C基因型母亲HBV DNA CpG岛的分布预测情况。39例HBV C基因型母亲中，19例在宫内传播组，20例在对照组。39例C基因型患者的HBV DNA有传统CpG岛Ⅱ和Ⅲ，而对照组有传统CpG岛Ⅰ和新的CpG岛Ⅳ和Ⅴ。宫内传播组CpG岛Ⅱ和Ⅲ的长度及CpG岛Ⅱ的CG位点数量与对照组不同（<0.05）。宫内传播组中CpG岛Ⅱ长度≥518 bp且CG位点数量≥40的比例（11/19）显著高于对照组（2/20）（<0.05）。X基因启动子区（Xp区）CpG岛Ⅱ的长度及CG位点数量高于对照组（<0.05）。在HBV宫内传播组中，大多数母亲（12/19）的HBV DNA CpG岛Ⅱ完全覆盖Xp区，显著高于对照组（5/2），且HBV DNA Xp区CG位点数量高于对照组（<0.05）。母亲C基因型HBV DNA CpG岛的分布与宫内传播有关。CpG岛Ⅱ的长度及CG位点数量可能增加HBV宫内传播的风险。
