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乙型肝炎表面抗原、抗体共阳性者的病毒基因组S区、基本核心启动子区和前C区变异分析
Variations of surface, basic core promoter and precore regions in genomes of HBV from chronic HBV-infected patients with positive for both HBs Ag and anti-HBs
【作者】 钱福初; 邹伟华; 秦基取; 李栋立; 范晓娴; 戴利成;
【Author】 QIAN Fu-chu;ZOU Wei-hua;QIN Ji-qu;LI Long-li;FAN Xiao-xian;DAI Li-cheng.;Huzhou Central Hospital;
【机构】 浙江省湖州市中心医院中心实验室; 浙江省湖州市中心医院检验科;
【摘要】 目的探讨HBsA g和抗-HBs共阳性患者HBV基因组S区、BCP区和前C区变异特点,了解该模式HBV感染者分子病毒学特征。方法慢性HBV感染者62例,其中血清HBs Ag和抗-HBs共阳性者27例,HBsA g单阳性者35例。对患者血清中的HBV基因组S区、基本核心启动子(BCP)区和前C区序列进行PCR扩增和测序,并对其变异位点进行分析。结果 HBsA g和抗-HBs共阳性组HBV基因组S区氨基酸突变率明显高于单阳性组,两者差异具有统计学意义(2.56%比1.26%,χ2=32.07,P<0.05);在a决定簇(aa124-147)尤其是第一个茎环内(aa124-137)氨基酸变异频率最高(4.76%比1.02%,χ2=11.58,P<0.05)。共阳性组患者HBV基因组BCP区A1762T/G1764A双突变发生率显著高于单阳性组(59.3%比28.6%,χ2=5.895,P<0.05);前C区A1846T变异也高于单阳性组(40.7%比17.1%,χ2=4.265,P<0.05)。同时共阳性组患者BCP区和前C区A1762T/G1764A+G1896A联合突变发生率也高于单阳性组(37.0%比14.3%,χ2=4.302,P<0.05)。结论 HBs Ag和抗-HBs共阳性患者HBV基因组S区a决定簇变异率、BCP区及前C区与肝癌发生相关位点变异发生率明显高于HBs Ag单阳性患者。
【Abstract】 Objective: The aim of this study is to analysis the variations of surface(S)region, basic core promoter(BCP) and precore(pre C) regions in genomes of HBV from chronic hepatitis B virus(HBV)-infected patients with coexistence of HBs Ag and anti-HBs. Methods: S region, BCP and pre C regions in genomes of HBV were amplified and sequenced in 62 HBV-infected patients including 27 HBs Ag-positive/anti-HBs-positive patients(double positive group) and 35 HBs Ag-positive/anti-HBs-negative patients(single positive group). The sequencing results and amino acid variants in these regions were analyzed. Difference of means between groups was compared by t test. Sample rate and variation rate were compared by chi-square test. Results: One hundred and fifty-six amino acids mutations within the S region were detected in 27 patients of double positive group and 100 mutations in 35 patients of single positive group. The mutation rate in double positive group was significantly higher than those in single positive(2.56% vs. 1.26%, χ2=32.07,P<0.05). The amino acid variants in double positive group were much higher than those in single positive group within major hydrophilic region(MHR), especially in the firstloop area of a-determinant in S region(4.76% vs. 1.02%, χ2=11.58,P<0.05). The mutation rate of A1762T/G1764 A in BCP in double positive group was significantly higher than those in single positive group(59.3% vs. 28.6%, χ2=5.895, P<0.05).The mutation rate of A1846 T in pre C region was higher in double positive group than those in single positive group(40.7% vs.17.1%, χ2=4.265,P<0.05). The mutation rate of A1762T/G1764 A + G1896 A in double positive group was also higher than that in single positive group(37.0% vs.14.3%, χ2=4.302, P<0.05). Conclusions: The mutation rates of S region, especially in the first loop area within a-determinant, BCP and pre C regions which are related with hepatocellular carcinoma(HCC) development in HBs Ag and anti-HBs double positive group are higher than those in HBs Ag single positive group in chronic HBV infected patients.
【Key words】 Hepatitis B virus; Hepatitis B surface antigen; Hepatitis B antibodies; Genes; Mutation;
- 【会议录名称】 2015年杭嘉湖感染性疾病学术年会暨国家级继续医学教育培训班论文汇编
- 【会议名称】2015年杭嘉湖感染性疾病学术年会暨国家级继续医学教育培训班
- 【会议时间】2015-10-30
- 【会议地点】中国浙江杭州
- 【分类号】R512.62
- 【主办单位】浙江省医师协会、杭州市西溪医院(市六医院)