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

Th 1免疫反应在干扰素治疗丙型肝炎时对HCV的清除以及慢性丙型肝炎患者肝细胞损伤的发展是必不可少的。骨桥蛋白是一种含有RGD序列的细胞外基质，是启动Th 1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发现了4个SNPs（nt-155，nt-433，nt-616，nt-1，748），发现nt-155，nt-616和nt-1，748的SNPs之间存在连锁不平衡，D'和r^2均大于0.937。用INVADER法检测了185例慢性丙型肝炎患者的SNPs等位基因。提示nt-433位点的SNP可能是反映慢性丙型肝炎患者肝炎活动性的一个标志物。另外，我们发现nt-155、nt-616和nt-1,748的SNP以及nt-433的SNP可以作为评估IFN治疗慢性丙型肝炎患者疗效的标记物，具有较高的阳性预测值。从这些数据我们得出结论，骨桥蛋白基因启动子区的SNP可能在调节抗HCV的Th 1免疫反应中起关键作用。

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.