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.

TH1免疫反应对于在干扰素治疗期间根除HCV以及在慢性丙型肝炎C的患者中的HCV以及肝细胞损伤的发育至关重要。骨桥蛋白是一种带有RGD序列的细胞外基质，是具有RGD序列的细胞外基质，对于th1免疫反应的开始是一种至关重要的细胞因子。最近，我们在Osteopontin Gene的启动子区域中确定了4个SNP（NT -155，-433，-616，-1,748），发现NT -155，NT -616和NT -1,748的SNP与D'和R^2大于0.937大于0.937的NT -616和NT -1,748显示出链接的不平衡。这些SNP的等位基因在185例慢性丙型肝炎患者中通过入侵分析确定。 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骨桥蛋白基因启动子区域中的SNP对于调节针对HCV的Th1免疫反应至关重要。

项目成果

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

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

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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)

Matsui A, Ohno A, Nagoshi S, Fujiwara K.: "Plasma Osteopontin Levels in Patients with Fulminant Hepatitis"Hepatology Research. (印刷中). (2004)

Matsui A、Ohno A、Nagoshi S、Fujiwara K.：“暴发性肝炎患者的血浆骨桥蛋白水平”肝病学研究（2004 年）。