IFN-γ+874和IL-2-330基因多态性在慢性HBV/HCV感染者临床转归中的交互作用  

Interaction of gene polymorphisms of IFN-γ+874 and IL-2-330 in the clinical regression of patients with chronic HBV/HCV infection

作　　者：张世勇[1] 袁阳 徐孟川 贾敏[3] 王丁军[1] 高秋菊 ZHANG Shiyong;YUAN Yang;XU Mengchuan;JIA Min;WANG Dingjun;GAO Qiuju(Center for Disease Prevention and Control of Shijiazhuang,Shijiazhuang,Hebei 050011,China;不详)

机构地区：[1]石家庄市疾病预防控制中心,河北石家庄050011 [2]陆军军医大学士官学校部队卫生防疫防护教研室 [3]河北省人民医院检验科

出　　处：《医学动物防制》2023年第8期791-793,共3页Journal of Medical Pest Control

基　　金：河北省科学技术研究与发展指导计划项目(07276139)。

摘　　要：目的探讨γ干扰素(interferon-γ,IFN-γ)基因+874位点和白介素-2(interleukin-2,IL-2)基因-330位点的基因多态性在慢性乙型肝炎病毒(Hepatitis B virus,HBV)和/或丙型肝炎病毒(Hepatitis C virus,HCV)感染者临床转归中的交互作用。方法对20世纪80年代末河北某农村单采血浆献血员中的HBV/HCV感染者进行分析,采用多因子降维法(multifactor dimensionality reduction method,MDR)分析IFN-γ+874和IL-2-330基因多态性在慢性HBV/HCV感染者临床转归中有无交互作用,风险评价用比值比(odds ratio,OR)和95%置信区间(confidence interval,95%CI)表示,交互作用评价指标主要为超额相对危险度(relative excess risk of interaction,RERI)、95%CI、交互作用指数(synergy index,SI)、交互作用归因比(attributable proportion of interaction,API)。结果①辅助性T细胞(helper T cell,Th cell)Th1类主要细胞因子IFN-γ+874、IL-2-330位点,对HBV/HCV感染者的临床不良转归有交互作用(P=0.001),检验准确度为0.6313,交叉验证一致性为10/10;②IFN-γ+874 AA和IL-2-330 TT基因型共存时,HBV/HCV感染者不良临床转归的OR值分别为10.13(2.25~45.68,轻型肝炎)、10.56(2.09~53.26,中重型肝炎)和13.57(2.18~84.37,肝硬化)差异有统计学意义(χ^(2)=19.84,P=0.02),分别是IFN-γ+874 AA基因型单独暴露时的6.80、4.06和8.13倍,是IL-2-330 TT基因型单独暴露时的8.37、8.06和6.56倍;③IFN-γ+874 AA和IL-2-330 TT基因型共存时,HBV/HCV感染者进展为轻型、中重型肝炎和肝硬化的交互作用指数(SI)分别为13.04、5.01和7.22;RERI分别为8.43(2.61~27.23)、7.65(2.50~23.42)和10.83(2.53~46.32);API分别为83.22%、72.44%和79.81%。结论慢性HBV/HCV感染者Th1类主要细胞因子IFN-γ+874 AA和IL-2-330 TT基因型共存时对HBV/HCV感染者的不良临床转归表现为协同交互作用。Objective To analyze the interaction of gene polymorphisms of the IFN-γgene+874 locus and IL-2 gene-330 locus in the clinical regression of patients with chronic Hepatitis B virus(HBV)and/or Hepatitis C virus(HCV)infection.MethodsThe interaction of the IFN-γ+874 and IL-2-330 gene polymorphisms in the clinical regression of chronic HBV/HCV-infected patients was analyzed by multifactor dimensionality reduction(MDR)in HBV/HCV-infected patients from a rural single plasma donor in Hebei in the late 1980s.The risk evaluation was expressed as odds ratio(OR)and 95%confidence interval(95%CI),and the interaction evaluating indicator were mainly the relative excess risk of interaction(RERI),95%CI,synergy index(SI),and attributable proportion of interaction(API).Results①Helper T cell(Th cell)class Th1 major cytokine IFN-γ+874 and IL-2-330 loci,interacted for adverse clinical regression in HBV/HCV-infected patients(P=0.001)with a test accuracy of 0.6313 and cross-validation agreement of 10/10.The ORs for adverse clinical regression in HBV/HCV-infected patients when IFN-γ+874 AA and IL-2-330 TT genotype were coexposed were 10.13(2.25-45.68,mild hepatitis),10.56(2.09-53.26,moderate to severe hepatitis),and 13.57(2.18-84.37,cihosis),respectively,the diflerencs were statistically significant(χ^(2)=19.84,P=0.02),which were 6.80,4.06 and 8.13 times higher than those for IFN-γ+874 AA genotype alone and 8.37,8.06 and 6.56 times higher than those for IL-2-330 TT genotype alone,respectively.③The progression to mild and moderate hepatitis and cirrhosis in HBV/HCV-infected patients when IFN-γ+874 AA and IL-2-330 TT genotypes were co-exposed synergy index(SI)was 13.04,5.01 and 7.22,respectively;RERI was 8.43(2.61-27.23),7.65(2.50-23.42),and 10.83(2.53-46.32),respectively.API was 83.22%,72.44%and 79.81%,respectively.Conclusion Chronic HBV/HCV-infected patients with Th1 major cytokines IFN-γ+874 AA and IL-2-330 TT genotypes exhibit a synergistic interaction for adverse clinical regression.

关 键 词：Γ-干扰素 白介素-2 细胞因子 HBV感染 HCV感染 临床转归 基因多态性 交互作用 

分 类 号：R512.6[医药卫生—内科学]