Studies on genomic polymorphisms determining host immune reactions against viral infection and interferon therapy

干扰素调节因子(IRF)-1在T辅助1 （Th1）细胞因子释放的功能激活中是不可或缺的。我们研究了IRF-1基因的启动子多态性（单核苷酸多态性；SNP），以了解SNP类型与对干扰素（IFN）治疗或宿主免疫反应的反应之间的相关性。根据宿主所拥有的SNP类型，宿主的免疫反应有显著差异。在具有一种SNP类型的宿主中，施用IFN可强烈激活Th1反应，而在具有另一种SNP类型的宿主中，Th2反应占优势。这些结果提示，通过检测IRF-1启动子SNP类型来预测HCV感染的宿主免疫反应是可能的，特别是在使用IFN治疗的慢性丙型肝炎患者中。因为Th1的功能有利于病毒的消除，而Th2的功能可能调节肝脏的炎症。然而，具有th1显性型的人很少，这种SNP类型不能解释患者对IFN治疗的反应。需要进一步的研究，包括其他各种细胞因子的启动子snp，以明确干扰素治疗对慢性丙型肝炎患者的准确预测。

Interferon regulatory factor (IRF)-1 has been indispensable for the functional activation of T helper 1 (Th1) cytokine release. We investigated promoter polymorphisms (single nucleotide polymorphisms ; SNPs) in the IRF-1 gene to see correlation between SNP types and response to the interferon (IFN) therapy or host immune reaction. Host immune reaction significantly differed according to the SNP types possessed by the host. Th1 reaction was strongly activated with administration of IFN in the host possessing one SNP type, but Th2 reaction was predominant in the host possessing the other type of SNP. These results suggested that the prediction of the host immune reaction in the HCV infection might be possible by checking IRF-1 promoter SNP types, especially in the patients with chronic hepatitis C treated with IFN. Because Th1 function is beneficial for viral elimination and Th2 function may regulate inflammation in the liver. However, the people with Th1-dominant type were few and this SNP types could not explain the response to IFN therapy in the patients. Further investigation including promoter SNPs in the other various cytokines is necessary for clarifying the exact prediction of the IFN therapy in patients with chronic hepatitis C.