IL-12A、IL-1B、IL-17A单核苷酸多态性与慢性乙型肝炎恩替卡韦治疗HBeAg血清学转换的遗传关联研究  

Association of IL-12A,IL-1B and IL-17A polymorphisms with HBe Ag seroconversion in chronic hepatitis B patients who received entecavir treatment

作　　者：吴俊秋[1] 何登明[2] 晏泽辉[1] 陶诗奇[1] 徐城[1] 朱鹏[1] 王宇明[1] 

机构地区：[1]第三军医大学西南医院全军感染病研究所、感染病研究重庆市重点实验室,重庆400038 [2]解放军第88医院全军肝病诊治中心,山东泰安271000

出　　处：《第三军医大学学报》2015年第9期839-844,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81270563)~~

摘　　要：目的通过遗传关联研究观察慢性HBV感染免疫相关重要细胞因子IL-12、IL-1B、IL-17的基因多态性与恩替卡韦抗病毒治疗HBe Ag血清学转换之间的关联。方法对109例恩替卡韦抗病毒治疗的HBe Ag阳性慢性乙型肝炎患者每3个月进行肝功能、乙肝标志物、HBV DNA检测,进行HBe Ag血清学转换评估,治疗24个月时的应答情况作为判定应答与否的标准。发生HBe Ag血清学转换者为应答组;未发生HBe Ag血清学转换者为无应答组;分析IL-12A rs568408、IL-1B rs1143623、IL-17A rs8193036基因型与HBe Ag血清学转换之间的关联。结果 29例获得HBe Ag血清学转换（应答组）,80例未获得HBe Ag血清学转换（无应答组）,总体应答率26.6%。IL-12A rs568408与HBe Ag血清学转换显著相关,GA基因型发生HBe Ag血清转换的易感性显著高于GG基因型[OR=3.72（1.34~10.32）,P=0.012]。未发现IL-1B rs1143623[OR=1.99（0.72~5.44）,P=0.17]和IL-17A rs8193036[OR=1.54（0.32~7.33）,P=0.60]与HBe Ag血清学转换存在关联。结论 IL-12A rs568408与慢性乙型肝炎恩替卡韦治疗HBe Ag血清学转换存在关联。Objective To investigate the effect of polymorphisms of IL-12, IL-1B and IL-17 on the response of antiviral treatment in chronic hepatitis B patients who received entecavir treatment, and explore the association of the polymorphisms with HBeAg seroconversion. Methods A total of 109 HBeAg-positive chronic hepatitis B patients who had received entecavir treatment in our department from October 2010 to August 2011 were prospectively recruited in this study. Their liver functions, HBV markers, and HBV copies were measured in every 3 months to evaluate HBeAg seroconversion. After 24 months＇ treatment, the cases achieving HBeAg seroconversion （response） were assigned as response group, and the others were assigned as non-response group. IL-12A rs568408, IL-1B rs1143623, and IL-17A rs8193036 were genotyped by MGB- TaqMan SNP genotyping assay. Then SNPstats was applied to analyze the association between the polymorphisms with HBeAg seroconversion. Results There were 29 cases getting HBeAg seroeonversion, and the other 80 cases not, with a total response rate of 26.6%. IL-12A rs568408 was associated with HBeAg seroconversion, with GA genotype achieving higher HBeAg seroconversion rate than GG genotype （OR = 3.72, 95% CI= 1.34- 10.32, P =0.012）. However, no significant association was found between IL-1B rs1143623 （OR=1.99, 95% CI=0.72 -5.44, P=0.17） or IL-17A rs8193036 （0R=1.54, 95% CI= 0. 32 - 7.33, P = 0.60） with HBeAg seroconversion. Conclusion IL-12A rs568408 is significantly associated with HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients who received entecavir treatment.

关 键 词：乙型肝炎 慢性 恩替卡韦 单核苷酸多态性 HBEAG血清学转换 

分 类 号：R392.2[医药卫生—免疫学] R512.62[医药卫生—基础医学]