Genetic Polymorphisms in Promoter Regions of Osteopontin Gene as Host Factors to Determine Th1 Immune Reactions against Hepatitis Virus.

Th1免疫反应是干扰素治疗期间根除丙型肝炎病毒和慢性丙型肝炎患者肝细胞损伤的关键，骨桥蛋白是一种具有RGD序列的细胞外基质，是启动Th1免疫反应的关键细胞因子。最近，我们在骨桥蛋白基因启动子区域发现了4个SNPs(-155、-433、-616、-1,748)，发现它们与D‘和r^2的连锁不平衡程度大于0.937。采用入侵者分析法检测185例慢性丙型肝炎患者的SNPs等位基因。同时，我们发现NT-155、NT-616和NT-1,748位SNP以及NT-433位SNP可以作为评价慢性丙型肝炎患者干扰素治疗疗效的标志物，具有较高的阳性预测值。

Th1 immune reaction is essential for eradication of HCV during interferon (IFN) therapy as well as development of hepatocyte injury in patients with chronic hepatitis C. Osteopontin, an extracellular matrix with RGD sequence, is a cytokine crucial for the initiation of Th1 immune reaction. Recently, we identified 4 SNPs (nt -155, -433, -616, -1,748) in the promoter region of osteopontin gene, and found that SNPs at nt -155, nt -616 and nt -1,748 showed linkage disequilibrium with D' and r^2 greater than 0.937 to each others. Alleles of these SNPs were determined in 185 patients with chronic hepatitis C by INVADER assay. We demonstrated that SNP at nt -433 may be a marker to reflect hepatitis activity in patients with chronic hepatitis C. Also, we found that SNPs at nt -155, nt -616 and nt -1,748 as well as SNP at nt -433 may be useful as markers to estimate efficacy of IFN therapy with high positive predictive value in chronic hepatitis C patients From these data, we concluded that SNPs in promoter region of osteopontin gene may be crucial in regulation of Th1 immune reaction against HCV.