【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0.631 3,交叉验证一致性为10/10;(2)IFN-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；(3)IFN-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。更多还原

【Abstract】 Objective To analyze the interaction of gene polymorphisms of the IFN-γ gene +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.Methods The 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).Results(1)Helper 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 0.631 3 and cross-validation agreement of 10/10.(2)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,cirrhosis),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.(3)The 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.更多还原