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

骨桥蛋白基因启动子区的遗传多态性作为宿主因素确定针对肝炎病毒的 Th1 免疫反应。

• 批准号: 14370191
• 负责人: FUJIWARA Kenji
• 金额: $ 4.35万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370191/
• 关键词: Osteopontin; SNP; Th1 immune reaction; Cytokine; Chronic hepatitis C; Auto immune hepatitis; Interferon; Hepatitis activity; オステオポンチン; サイトカイン

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.

在干扰素（IFN）治疗期间，Th1免疫反应对于HCV的根除以及慢性丙型肝炎患者肝细胞损伤的发展至关重要。骨桥蛋白是一种具有RGD序列的细胞外基质，是Th1免疫反应启动的关键细胞因子。最近，我们在骨桥蛋白基因启动子区鉴定了4个snp (nt -155、-433、-616、- 1748)，发现nt -155、nt -616和nt - 1748位点的snp存在连锁不平衡，且D′和r^2的比值大于0.937。用INVADER法测定185例慢性丙型肝炎患者的这些snp等位基因。我们证明了SNP在nt -433可能是一个标志,以反映在慢性丙型肝炎患者肝炎活动,我们发现,单核苷酸多态性在-155元,-616元和-1748元以及SNP在-433元作为疗效标记来估计可能有用高阳性预测值的干扰素治疗慢性丙型肝炎患者从这些数据,我们得出的结论是,骨桥蛋白基因的启动子区域的单核苷酸多态性可能对丙肝病毒Th1调节免疫反应的关键。

项目成果

Extrahepatic manifestations in transgenic mice of osteopontin in hepatocytes - A clue to advent of pathological state in various organs of chronic hepatitis C patients

• DOI: 10.1016/j.hepres.2005.01.010
• 发表时间: 2005-04-01
• 期刊: HEPATOLOGY RESEARCH
• 影响因子: 4.2
• 作者: Saitoh, E;Matsui, A;Fujiwara, K
• 通讯作者: Fujiwara, K

Transgenic mice expressing osteopontin in hepatocytes as a model of autoimmune hepatitis

• DOI: 10.1016/j.bbrc.2004.02.180
• 发表时间: 2004-04-23
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Mochida, S;Yoshimoto, T;Fujiwara, K
• 通讯作者: Fujiwara, K

Fujiwara K, Mochida S.: "Indication and criteria for liver transplantation for fulminant hepatic failure"Journal of Gastroenterology. 37. 74-77 (2002)

Fujiwara K，Mochida S.：“暴发性肝衰竭肝移植的适应症和标准”胃肠病学杂志。

Massive liver necrosis after provocation of imbalance between Th1 and Th2 immune reactions in osteopontin transgenic mice

• DOI: 10.1007/s00535-004-1403-0
• 发表时间: 2004-09-01
• 期刊: JOURNAL OF GASTROENTEROLOGY
• 影响因子: 6.3
• 作者: Mimura, S;Mochida, S;Fujiwara, K
• 通讯作者: Fujiwara, K

藤原研司, 持田 智: "肝炎劇症化の機序<Editorial>"肝臓. 43. 341-351 (2002)

Kenji Fujiwara、Satoshi Mochida：“暴发性肝炎的机制<社论>”肝脏。43. 341-351 (2002)