HBeAg阴性慢性乙型肝炎患者B、C基因型HBV S蛋白变异比较

Comparison of mutation rate of HBV S protein between genotype B and C in HBeAg negative chronic hepatitis B patients

目的探讨乙型肝炎病毒(hepatitis B virus,HBV)基因型与S蛋白变异的关联,为分析病毒基因型在疾病预后转归中的作用提供理论基础。方法选择上海中医药大学附属曙光医院东院2019年1月至2019年10月门诊或住院的HBeAg阴性慢性乙型肝炎患者99例,其中,B基因型50例,C基因型49例。基因测序法用于S蛋白基因序列分析,分类变量间差异分析采用χ^(2)检验与连续校准。非正态分布数据采用非参数秩和检验。结果HBeAg阴性慢性乙型肝炎组C基因型的S蛋白变异率高于B基因型为87.76%(43/49)比66.00%(33/50),(χ^(2)=6.567,P=0.010),且变异差异位点似乎为随机分布,主要亲水区(major hydrophilic region,MHR)与MHR外的变异率,C基因型均高于B基因型为38.78%(19/49)比18.00%(9/50),(χ^(2)=5.266,P=0.022);85.71%(42/49)比56.00%(28/50),(χ^(2)=10.550,P=0.001)。两基因型MHR的“a”决定簇[32.65%(16/49)比12.00%(6/50),(χ^(2)=6.107,P=0.013)]以及MHR外的细胞毒T淋巴细胞+辅助性T淋巴细胞(CTL+Th)免疫表位[69.39%(34/49)比40.00%(20/50),(χ^(2)=8.620,P=0.003)]与非免疫表位[53.06%(24/49)比30.00%(15/50),(χ^(2)=5.424,P=0.020)]差异均有统计学意义。结论HBeAg阴性慢性乙型肝炎患者C基因型较B基因型更容易产生HBV S蛋白变异。

Objective To investigate the association between hepatitis B virus(HBV)genotype and S protein mutations and to provide a theoretical basis for analyzing the role of viral genotype in the prognosis of disease.Methods Ninty-nine HBeAg negative chronic hepatitis B(CHB)patients admitted to our hospital from January 2019 to October 2019 were enrolled in this study,the number of genotype B and genotype C were 50 and 49,respectively.DNA sequencing was used to detect the gene sequence of HBV S protein.Differences between categorical variables were analyzed by Chi-square test and Continuity Correction.Non-parametric test(Mann-Whitney U)was used for analyzing non-normal distribution data.Results The mutation rate of S protein in genotype C group was significantly higher that of the genotype B group(87.76%vs.66.00%,χ^(2)=6.567,P=0.010),furthermore,the mutation sites were distributed randomly,mutation rates in both major hydrophilic region(MHR)and outside the MHR of genotype C were higher than that of genotype B(38.78%vs.18.00%,χ^(2)=5.266,P=0.022;85.71%vs.56.00%,χ^(2)=10.550,P=0.001 respectively).In addition,statistical differences were also found in the“a”determinant(32.65%vs.12.00%,χ^(2)=6.107,P=0.013)located in MHR and immune epitopes(69.39%vs.40.00%,χ^(2)=8.620,P=0.003)and nonimmune epitopes(53.06%vs.30.00%,χ^(2)=5.424,P=0.020)of cytotoxic T lymphocytes+T-helper cell(CTL+Th)located outside the MHR between the genotype C and B.Conclusion Genotype C was more prone to HBV S protein mutations than genotype B among HBeAg negative CHB patients.