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目的了解住院孕妇显性和隐匿性乙型肝炎病毒感染(OBI)及其病毒株S基因分子进化特征。方法采用以医院为基础的住院孕妇队列研究,招募2012年6月1日—2013年3月15日医院产科孕妇1 130人,收集人口学资料和血清,并采用罗氏电化学发光法检测乙型肝炎病毒表面抗原(HBsA g)及巢式PCR进行HBV S片段的扩增并测序,分析并比较住院孕妇显性乙型肝炎病毒(HBV)感染与OBI的人口学分布特征及S区序列变异。结果在1 130名孕妇中,HBV感染比例为16.55%,其中显性HBV感染和OBI的比例分别为8.4%和8.1%。共获得136株HBV S基因序列,其中基因C型17株,基因B型119株。与基因B型显性HBV株相比,OBI株出现更高的核苷酸和氨基酸替换率,8个核苷酸位点出现统计学显著的次要等位基因频率,并导致HBV S基因和对应的HBV P基因出现非同义氨基酸替换,分别为5个(G44E、T126A、R129Q、W156L和Y200F)和4个(I438L、K478N/D、N481S/D和L511F)。此外,3例OBI出现W35终止码替换,1例OBI出现第123位和第124位点的插入替换。结论住院孕妇存在较高的HBV感染比例,OBI与显性HBV感染比例大致相当;B基因型OBI株出现统计显著的核苷酸和/或氨基酸位点替换,可能与OBI的发病机制有关。
Objective To understand the dominant and occult hepatitis B virus (OBI) in hospitalized pregnant women and the molecular evolution characteristics of S gene of the virus. Methods A hospital-based cohort of hospitalized pregnant women was enrolled in this study. A total of 1,130 obstetric women were enrolled in the hospital from June 1, 2012 to March 15, 2013. Demographic data and serum were collected and detected by Roche electrochemiluminescence Hepatitis B virus surface antigen (HBsA g) and nested PCR were used to amplify and sequence HBV S fragments. The demographic distribution and S region sequence variation of dominant hepatitis B virus (HBV) infection and OBI in hospitalized pregnant women were analyzed and compared. Results Among 1130 pregnant women, the proportion of HBV infection was 16.55%, and the ratio of dominant HBV infection to OBI was 8.4% and 8.1% respectively. A total of 136 HBV S gene sequences were obtained, of which 17 were C-type gene and 119 B-type gene. OBI strains showed higher nucleotide and amino acid substitution rates than genotype B dominant HBV strains with a statistically significant minor allele frequency at 8 nucleotide sites and led to a higher HBV S gene and The corresponding non-synonymous amino acid substitutions were found in the HBV P gene, 5 (G44E, T126A, R129Q, W156L and Y200F) and 4 (I438L, K478N / D, N481S / D and L511F), respectively. In addition, 3 cases of OBI appeared W35 termination code replacement, 1 case of OBI appear 123rd and 124th place insertion replacement. Conclusions There is a high proportion of HBV infection in hospitalized pregnant women. The ratio of OBI to dominant HBV infection is approximately the same. Statistical significance of nucleotide and / or amino acid substitutions is found in the OB genotype of B genotype, which may be related to the pathogenesis of OBI.