乙型肝炎病毒基因型和前C及基本核心启动子突变与乙型肝炎疫苗阻断母婴传播的关系

目的探讨乙型肝炎（乙肝）病毒（HBV）基因型和前C及基本核心启动子（BCP）突变与乙肝疫苗阻断母婴传播的关系。方法采集江苏省16对乙肝疫苗阻断失败的母婴血清样本32份,以及88对阻断成功的母婴血清样本176份。以型特异性引物PCR法检测16对乙肝疫苗阻断失败的母婴和88例阻断成功的母亲血清样本中HBV基因型,用PCR产物直接测序法检测HBV前C/ BCP突变,采用Clustal W 1．8软件进行序列分析。结果在16例阻断失败的母亲中,15例（93．8%）为HBeAg阳性,且均为C型（15/15,100%）;88例阻断成功的母亲中,51例（58．0%）为HBeAg阳性,其中C基因型占45．1%（23／51）。在HBeAg阳性母亲中,阻断失败组的C基因型检出率明显高于阻断成功组（X~2=14．3,P=0．003）。但在C基因型HBeAg阳性母亲中,阻断成功组与失败组的T1762/ A1764突变率差异无统计学意义（分别为13．3%和33．3%,P=0．4）,且均无A1896突变。结论感染HBV基因C型的母亲可能更易导致乙肝疫苗阻断失败,而前C/BCP基因突变与阻断母婴传播无关。

Interruption failure of heptitis B virus vaccination in mother-to-infant transmission and heptitis B virus genotypes and preC/BCP mutations

OBJECTIVE: To investigate the association of heptitis B virus (HBV) genotypes and precore(PreC)/basal core promoter(BCP) mutation with interruption failure of HBV vaccination in mother-to-infant transmission. METHODS: A total number of 208 serum samples were collected from infants and mothers,including 16 infants who had become HBsAg-positive despite a complete and timely course of immunization and another 88 infants successfully protected from mother-to infant HBV transmission. HBV genotypes were determined by type-specific primers PCR method. PreC/BCP mutations were detected by direct sequencing of PCR products, and Clustal W 1.8 software was applied to analyzing the sequences. RESULTS: Of 16 mothers who were having vaccine failure infants, 15 (93.8%) were HBeAg positive and infected with genotype C (15/15, 100%). Among 88 mothers of having children being protected by vaccine, 51 (58.0%) were HBeAg positive, with 45.1% (23/51) of genotype C. The proportion of genotype C in HBeAg mothers of infants with vaccine failure, was significantly higher than that of mothers with vaccine protected infants (chi2 = 14.3, P = 0.003). However, the frequencies of T1762/A1764 mutations had no significant differences between genotype C HBeAg positive mothers with vaccine failure or protected infants (33.3% and 13.3%, respectively, P = 0.4). No A1896 mutation was found in these two groups. CONCLUSION: HBV genotype C might contribute to the immune failure of HBV vaccination in mother-to-infant transmission, while PreC/BCP mutation might not have correlation with it.