HCVF蛋白和APC基因甲基化与慢性HCV感染的相关研究  

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

作　　者：季晓伟[1] 肖雯[2] 裴家平 石丽萍[1] 蒋龙凤[3] 王长军[2] 邓小昭[1,2] 张琪[2] 韩一芳[2] 张锦海[2] 朱丹燕[1] 徐孝东[1] Ji Xiao-wei XIAO Wen PEI Jia-ping SHI Li-ping JIANG Long-feng WANG Chang-jun DENG Xiao-zhao ZHANG Qi HAN Yi- fang ZHANG Jin-hai ZHU Dan-yan XU Xiao-dong(Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing 210029, China Institute of Disease Control and Prevention, Center for Disease Control and Prevention of Nanjing Command, First Affiliated Hospital of Nanjing Medical University, Nanjing Nanjing 210002, China Department of lnfection, the 210029, China)

机构地区：[1]南京医科大学基础医学院生物化学与分子生物学系,江苏南京210029 [2]南京军区疾病预防控制中心疾病预防控制所,江苏南京210002 [3]南京医科大学第一附属医院感染病科,江苏南京210029

出　　处：《中华疾病控制杂志》2017年第4期327-331,共5页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(81573213;81172724);江苏省自然科学基金(BK20151089;BK20161059;BL2013021);中国肝炎基金会天晴肝病研究基金(CFHPC20132071)

摘　　要：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。Objective To investigate the relationship between F protein and the methylation 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.

关 键 词：基因 APC 甲基化 肝炎病毒属 

分 类 号：R512.63[医药卫生—内科学]