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 免疫反应对于干扰素 (IFN) 治疗期间 HCV 的根除以及慢性丙型肝炎患者肝细胞损伤的发生至关重要。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鉴定了4个SNP（nt -155、-433、-616、-1,748），发现nt -155、nt -616和nt -1,748处的SNP与D'存在连锁不平衡。 r^2 彼此之间大于 0.937。通过 INVADER 测定在 185 名慢性丙型肝炎患者中确定了这些 SNP 的等位基因。我们证明，nt -433 处的 SNP 可能是反映慢性丙型肝炎患者肝炎活动的标志物。此外，我们发现 nt -155、nt -616 和 nt -1,748 处的 SNP 以及 nt -433 处的 SNP 可能是反映慢性丙型肝炎患者肝炎活动的标志物。可以作为评估慢性丙型肝炎患者 IFN 治疗疗效的标志物，具有高阳性预测价值。从这些数据中，我们得出结论，骨桥蛋白基因启动子区域的 SNP 可能在调节针对 HCV 的 Th1 免疫反应。

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）。