干扰素应答相关基因芯片在预测丙型肝炎抗病毒疗效中的应用研究

目的 探讨干扰素（IFN）应答相关基因在预测丙型肝炎抗病毒疗效中的作用.方法 采用功能分类基因芯片方法对IFN治疗前慢性丙型肝炎患者外周血单个核细胞（PBMC）IFN相关基因的表达进行检测,结合临床资料进行分析.采用SPSS 12.0软件进行统计学处理.结果 17例慢性丙型肝炎患者中,IFN治疗快速病毒学应答者（RVR）10例,非快速病毒学应答者（N-RVR）7例.与健康对照组比较,RVR患者PBMC中发现9个差异表达基因,其中1个为上调基因,8个为下调基因;N-RVR患者有18个差异表达基因,均为下调基因.RVR与N-RVR患者比较,发现5个差异表达基因,其中4个为上调基因,分别为PRKCZ、PRKRA、IRF5和TNFSF10（t=5.44、3.13、5.24和2.30,P=0.000、0.010、0.005和0.044）,1个下调基因为IFIT5（t=2.43,P=0.035）.17例患者中,12例为HCV1b型,5例为HCV2a型,HCV1b型与HCV2a型患者比较,发现2个下调基因,分别为IFI6和IFI44（t=2.42和2.45,P=0.038和0.033）.结论 IFN应答相关基因下调可能与慢性丙型肝炎患者对IFN治疗的应答有关.HCV1b型患者比HCV2a型患者更容易诱导IFN相关基因表达的下调,从而产生IFN抵抗.

Interferon response-related gene array in predicting the outcome of antiviral treatment in chronic hepatitis C

Objective To explore the application of interferon（IFN）response-related genes in predicting the outcome of antiviral treatment in chronic hepatitis C. Methods SuperArray microarray was used to detect the expression of IFN response-related genes in peripheral blood monocytes（PBMC）from chronic hepatitis C patients before treatment. SPSS 12.0 was used for statistical analysis. Results Ten patients were classified as rapid responders（RVR）and seven patients as non-RVRs according to the serum HCV RNA level after 4 weeks of treatment in 17 patients. Compared with healthy controls, nine differentially expressed genes were found in RVR patients, one up-regulated and eight down-regulated; eighteen differentially expressed genes were found in N-RVR patients, all down-regulated. Five differentially expressed genes were found between the patients with RVR and N-RVR： four up-regulated genes were PRKCZ, PRKRA, IRF5 and TNFSF10（t =5.44, 3.13, 5.24 and 2.30, P=0. 000, 0.010, 0.005 and 0. 044）; one up-regulated gene was IFIT5（t = 2.43, P = 0. 035）. Of seventeen patients, 12 were HCV genotype 1b, 5 were HCV genotype 2a. Compared with HCV2a, IFI6 and IFI44 gene in HCV1b were downregulated（t = 2.42 and 2.45, P = 0. 038 and 0. 033）. Conclusions The expression of IFN responserelated genes is associated with response to IFN treatment. HCV genotype 1 b is more successful in inducing the down-regulation of IFN response-related genes than that of HCV genotype 2a, thus leading to the resistance to IFN.