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乙型肝炎表面抗体与表面抗原同时存在的慢性乙型肝炎携带者中前S/S基因突变的检测

Detection of pre-S/S gene mutants in chronic hepatitis B carriers with concurrent hepatitis B surface antibody and hepatitis B surface antigen.

作者信息

Wang Y M, Ng W C, Lo S K

机构信息

Department of Medicine, National University of Singapore, Singapore.

出版信息

J Gastroenterol. 1999 Oct;34(5):600-6. doi: 10.1007/s005350050379.

DOI:10.1007/s005350050379
PMID:10535488
Abstract

Hepatitis B virus (HBV) with various mutations has been reported. The frequency of the natural occurrence of such variants and whether the heterogeneity of these genomic regions correlates with a specific serologic pattern of concurrent hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were investigated. We analyzed the perS/S regions of HBV in six asymptomatic HBV carriers who were seropositive for both HBsAg and anti-HBs (group A), four hepatocellular carcinoma (HCC) patients with concurrent HBsAg and anti-HBs (group B), and five asymptomatic HBV carriers without anti-HBs as controls (group C). PreS/S regions of HBV-DNA were amplified by polymerase chain reaction (PCR), cloned, and sequenced. The results showed that, in some of the samples, a few deletions and numerous point mutations were presented in preS/S regions. One of the HBV carriers with anti-HBs (group A) and an HCC patient with anti-HBs (group B) had point mutations in the "a" determinant, resulting in conversion from Ile-126 of wild-type to Asn-126. The patients with anti-HBs (groups A and B) had a significantly greater divergence rate of amino acid for the preS/S gene compared with controls. Our results suggested that the HBV mutants observed in the preS/S gene may have led to changes in the immunogenicity of the viral particles, and thus influence the viral behavior and clinical course. Therefore, some HBV patients with concurrent HBsAg and anti-HBs may be HBV S mutants.

摘要

已报道了具有各种突变的乙型肝炎病毒(HBV)。研究了此类变体自然发生的频率,以及这些基因组区域的异质性是否与同时存在的乙型肝炎表面抗原(HBsAg)和乙型肝炎表面抗体(抗-HBs)的特定血清学模式相关。我们分析了6例HBsAg和抗-HBs均呈血清学阳性的无症状HBV携带者(A组)、4例同时存在HBsAg和抗-HBs的肝细胞癌(HCC)患者(B组)以及5例无抗-HBs的无症状HBV携带者作为对照(C组)的HBV的前S/S区域。通过聚合酶链反应(PCR)扩增、克隆并测序HBV-DNA的前S/S区域。结果显示,在一些样本中,前S/S区域存在一些缺失和大量点突变。1例有抗-HBs的HBV携带者(A组)和1例有抗-HBs的HCC患者(B组)在“a”决定簇中有点突变,导致从野生型的Ile-126转换为Asn-126。与对照组相比,有抗-HBs的患者(A组和B组)前S/S基因的氨基酸分歧率显著更高。我们的结果表明,在前S/S基因中观察到的HBV突变体可能导致病毒颗粒免疫原性的变化,从而影响病毒行为和临床病程。因此,一些同时存在HBsAg和抗-HBs的HBV患者可能是HBV S突变体。

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