宫内传播中乙型肝炎病毒前S/S基因序列分析

Sequencing analysis of preS/S gene of hepatitis B virus in intrauterine transmission

目的 研究宫内传播中乙型肝炎病毒 (HBV)的前S/S基因结构 ,探讨HBV基因变异与宫内传播的关系。方法 根据新生儿发生HBV宫内感染与否 ,将其HBsAg阳性母亲分为宫内感染组和非宫内感染组 ,经PCR扩增HBV前S/S基因 2 848- 835位核苷酸序列 ,克隆、测序 ,比较 2组基因结构的差异。结果 全部HBV株序列都属于C基因亚型、adr亚型 ,宫内感染组中母婴序列的相似性达 99.2 %～ 1 0 0 .0 %。 2组患者在前S1区、前S2区和S区均有各自的突变位点 ,S区“a”决定簇表位几乎没有突变发生。非宫内感染组中nt2 90 9、nt399、nt2 93和nt483突变出现较多 ,而在宫内感染组尤其是新生儿的序列中出现较少。而且非宫内感染组前S2区 (P <0 .0 5)、S区 (P <0 .0 1 )和前S/S区 (P <0 .0 5)突变率也高于宫内感染组。结论 引起新生儿宫内感染的HBV前S/S基因异质性较低 。

Objective To investigate the relationship between HBV intrauterine transmission and gene variation by analysis of HBV PreS/S gene sequence in intrauterine transmission.Methods According to whether neonate was infected by HBV in uterus,their HBsAg positive mothers were divided into intrauterine infection group and non-intrauterine infection group.PreS/S gene nt2848-835 of HBV was amplified by polymerase chain reaction (PCR),then the PCR products were cloned and sequenced.The sequences were compared with each other between groups.Results All HBV sequences were genotype C and subtype adr.The nucleotide similarity were 99.2%-100% between the mother and her neonates.In every case,there were several mutations in preS1,preS2,and S regions,respectively.Almost no significant mutation was found in 'a' determinant of S gene.The mutation rate positions nt2909,nt399,nt293 and nt483 in non-intrauterine infection group was higher than that of intrauterine infection group.The mutation rates in preS2,S,and preS/S region were also higher in non-intrauterine infection group.Conclusion The preS/S gene heterogeneity of HBV strains which can infect neonate in uterus was lower.The results suggest that the strains of HBV with lower mutation rate in PreS/S gene can cause intrauterine infection easily.