HCV F蛋白和APC基因甲基化与慢性HCV感染的相关研究

目的 探讨丙型肝炎病毒（hepatitis C virus，HCV）F蛋白与多发性腺瘤样息肉病（adenomatous polyposis coli，APC）基因甲基化在慢性HCV感染中的关系。方法 收集慢性HCV患者（chronic hepatitis patient，CHP）的血样，检测F抗体（F antibody，F-Ab）的阳性率并且分成两组（F-Ab（+）CHP组、F-Ab（-）CHP组），收集健康者的血样作为对照组；分离外周血单核细胞（peripheral blood mononuclear cells，PBMCs），分别用HCV Core/F蛋白刺激，72 h后，分别提取DNA，用二代测序检测APC基因的甲基化水平，分析各组APC基因甲基化程度的差异。结果 APC基因甲基化程度在F-Ab（+）CHP组、F-Ab（-）CHP组及健康对照组三组间差异有统计学意义（F=185.185，P<0.001），F-Ab（+）CHP组APC基因甲基化程度高于F-Ab（-）CHP组，健康对照组最低（均有P<0.05）；三组样本PBMC分别经Core/F蛋白体外刺激后，APC基因甲基化程度各组总体比较差异均有统计学意义（均有P<0.05），Core蛋白与F蛋白共刺激组细胞APC基因甲基化程度高于F蛋白刺激组，Core蛋白刺激组为最低。结论 在慢性HCV感染患者中，HCV F蛋白的产生能够影响APC基因甲基化程度。

Association between F protein and the methylation of APC gene in chronic HCV infection

Objective To investigate the relationship between F protein and the methvlation of adenomatous polyposis coli (APC) gene in chronic hepatitis C virus (HCV) infection.Methods Blood samples collected from chronic HCV patients (CHP) were divided into F-Ab(+) CHP group and F-Ab(-) CHP group,blood samples from healthy persons were used as control.Isolated peripheral blood mononuclear cells (PBMCs) were stimulated by Core protein and F protein for 72 hours,and then cell DNA was etracted to detect the methylation level of APC gene.Results The methylation level of APC gene in three groups was significantly different (F =185.185,P ＜ 0.001),The methylation level of APC gene in FAb(+) CHP group was significantly higher than that in F-Ab (-) CHP group,the healthy control group was the lowest (all P ＜ 0.05).There was significant difference in methylation level of APC gene by Core / F protein stimulated in vitro in all subgroups(all P ＜ 0.05).The methylation of APC gene in cells stimulated by Core protein and F protein was higher than that in cells stimulated by F protein,which was higher than that in cells stimulated by Core protein.Conclusions HCV F protein can affect the methylation of APC gene in chronic HCV infection.