家系感染乙型肝炎病毒基因变异与HLA-Ⅱ类等位基因的关系

The relationship between HBV gene mutation in HBV infected family and HLA class Ⅱ alleles

目的研究家系内慢性乙型肝炎病毒基因变异特征及与HLA-II类分子基因多态性的关系。方法采用PCR扩增和产物测序检测HBV前C区1896位及BCP区1762/1764位变异,分析家系内慢性HBV感染者121例(实验组)病毒变异特征及与非家系慢性乙肝患者83例(对照组)病毒变异频率差异;用PCR/SSP对家系内慢性HBV感染者的HLA-DQA1和DQB1等位基因多态性进行测定;分析HLA-II类分子基因多态性与家系内慢性乙型肝炎病毒基因变异的关系。结果实验组前C区1896位变异、BCP区1762/1764位双变异及联合变异率均高于对照组;HLA-DQA1*0501和DQB1*0301等位基因频率和家系慢性HBV感染者前C区1896位、BCP区1762/1764位及联合变异有关;母亲为第一代的感染家系中,子女的前C区1896位及BCP区1762/1764位变异与母亲是否有该位点变异差异无显著性。结论家系感染HBV患者中,HBV前C区1896位、BCP区1762/1764位双突变及联合变异频率明显高于无家系感染的慢性乙型肝炎患者;家系内感染HBV前C区1896位、BCP区1762和1764位变异并非都是由上一代遗传或传播而来,而主要是与个体的免疫状况有关。

Objective To study the relationship between the characteristics of mutation in hepatitis B virus（HBV） infected family and HLA class II molecular genetic polymorphism.Methods The mutations of HBV pre-Core area 1896 and the basal core promoter（BCP） 1762/1764 were amplified and sequenced.The characteristics and frequencies of the two site mutations of HBV were analyzed in 121cases of infected family（experimental group） and 83 cases with chronic hepatitis B（control group） of non-infected family.The HLA-DQA1 and DQB1 alleles were tested using PCR/SSP.The relationship between the HLA-II polymorphism in（HBV） infected family and HBV gene mutation was analyzed.Results The variations of pre-Core area 1896,and BCP area 1762/1764 in experimental group were higher than the control group.Combination mutations in HLA-DQA1＊0501and DQB1＊0301 alleles,and HBV pre-Core area 1896 and BCP1762/1764 were found in the experimental group.In the mothers of HBV infected families as the first generation,the mutations in HBV pre-Core area 1896 and BCP1762/1764 of the offspring has no relationship.Conclusion The pre-Core area 1896 and BCP area 1762/1764 mutations of HBV combined with HLA-DQA1＊0501 and DQB1＊0301 frequencies in family infection cases were significantly higher than those patients without family infection.There may be a relationship between the pre-Core area 1896 and BCP area 1762/1764 mutations and the immune status