乙型肝炎病毒C基因启动子区及前C区突变与乙型肝炎病情的关系

目的分析乙型肝炎病毒(HBV)C基因启动子(BCP)双突变及前C区nt1896位点突变与乙型肝炎临床表现及e抗原(HBeAg)表型的关系。方法采用巢式聚合酶链反应(PCR)扩增nt1660~1935的HBVDNA片段及PCR产物直接测序的方法检测BCP区及前C区基因的变异情况。结果130例经证实为HBVDNA阳性的急慢性肝炎患者中共有75例BCP区nt1762、nt1764双突变,HBeAg阳性组BCP突变者32例(58.2%),而HBeAg阴性组43例(57.3%)。检出前C区nt1896突变者20例,其中慢性肝炎10例(12.8%)、重型肝炎2例(25.0%)、肝硬化8例(22.2%);nt1896突变者在HBeAg阳性组3例(5.5%),HBeAg阴性组17例(22.7%),两组比较差异有统计学意义。nt1896突变组丙氨酸转氨酶(ALT)及HBV DNA水平较无突变组差异均有统计学意义。结论BCP双突变及前C nt1896均与肝炎的慢性化、重型化及肝硬化的发生密切相关,前者对HBeAg的表达及HBV-DNA水平并无明显影响;后者影响HBeAg的表达,并且增强病毒复制水平。

The relationship between the progression of chronic Hepatitis B and the gene mutations in the regions of basic cone promoter and the pre-core

Objective To investigate the gene mutations in the regions of basic core promoter(BCP) and pre core/core(Pre C/C) of HBV DNA and its clinical significance.Methods The nt1660～1935 segment of HBV-DNA was amplified with nest PCR in 130 cases with hepatitis B.Then the PCR products were sequenced.Results Seventy-five cases of nt1762/1764 double mutations were detected in 130 patients with hepatitis B.Thirty-two cases(58.2%) and 43 cases(57.3%) of BCP double mutation were detected in the HBeAg positive group and HBeAg negative group respectively.Twenty cases of Pre-C nt1896 mutation composed of CH 10 cases(12.8%),SH 2 cases(25.0%) and LC 8 cases(22.2%) were detected in 130 cases.Three cases(5.5%) and 17 cases(22.7%) Pre-C nt1896 mutations were detected in the HBeAg positive group and HBeAg negative roup respectively.The levels of ALT and HBV DNA in the Pre-C mutation group were higher than those in the wild type group.Conclusion BCP nt1762/1764 double mutation and the Pre-C nt1896 mutation are both closely related to the progression of chronic liver disease.nt 1762/1764 double mutation did not affect the expression of HBeAg and the ALT level whereas the Pre-C nt1896 mutation did.