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

Research Project

Project/Area Number 14370191
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSaitama Medical School

Principal Investigator

FUJIWARA Kenji  Saitama Medical School, Department of Medicine, Professor, 医学部, 教授 (80101088)

Co-Investigator(Kenkyū-buntansha) MOCHIDA Satoshi  Saitama Medical School, Department of Medicine, Professor, 医学部, 教授 (20219968)
NAGOSHI Sumiko  Saitama Medical School, Department of Medicine, Associate Professor, 医学部, 助教授 (50306271)
MATSUI Atsushi  Saitama Medical School, Department of Medicine, Assistant Professor, 医学部, 講師 (40260484)
INAO Mie  Saitama Medical School, Department of Medicine, Assistant Professor, 医学部, 講師 (70286037)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥3,600,000 (Direct Cost: ¥3,600,000)
KeywordsOsteopontin / 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
Research Abstract

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.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (32 results)

All 2005 2004 2003 Other

All Journal Article (17 results) Patent(Industrial Property Rights) (2 results) Publications (13 results)

  • [Journal Article] SNPs in the Promoter Region of Osteopontin Gene as a Marker Predicting the Efficacy of Interferon-Based Therapies in Chronic Hepatitis C.2005

    • Author(s)
      Naito M, Matsui A, Inao M, Nagoshi S, et al.
    • Journal Title

      Journal of Gastroenterology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Extrahepatic Manifestations in Transgenic Mice of Osteopontin in Hepatocytes : A Clue to Advent of Pathological State in Various Organs of Chronic hepatitis C Patients2005

    • Author(s)
      Saitoh E, Matsui A, Inao M, Mimura S, et al.
    • Journal Title

      Hepatology Research (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Extrahepatic Manifestations in Trausgenic Mice of Osteopontin in Hepatocytes : A Clue to Advent of Pathological State in Various Organs of Chronic Hepatitis C Patients2005

    • Author(s)
      Gaitoh E, Matsui A, Inao M, Mimura S, et al.
    • Journal Title

      Hepatology Research (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transgenic Mice Expressing Osteopontin in Hepatocytes as a Model of Autoimmune Hepatitis2004

    • Author(s)
      Mochida S, Yoshimoto T, Mimura S, Inao N, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 317

      Pages: 114-120

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genetic Polymorphisms in Promoter Region of Osteopontin Gene May be a Marker Reflecting Hepatitis Activity in Chronic Hepatitis C Patients2004

    • Author(s)
      Mochida S, Hashimoto M, Matsui A, Naito M, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 313

      Pages: 1079-1085

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Massive Liver Necrosis after Provocation of Imbalance between Th1 and Th2 Immune Reactions in Osteopontin Transgenic Mice2004

    • Author(s)
      Mimura S, Mochida S, Inao M, Matsui A, Nagoshi S, et al.
    • Journal Title

      Journal of Gastroenterology 39

      Pages: 867-872

    • NAID

      10013613344

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Japanese Harbel Medicine Inchin-Ko-To as a Therapeutic Drug for Liver Fibrosis2004

    • Author(s)
      Inao M, Mochida S, Matsui A, Eguchi Y, et al.
    • Journal Title

      Journal of Hepatology 41

      Pages: 584-591

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Genetic Polymorphisms in Promoter Region of Osteopontin Gene May be a Marker Reflecting Hepatitis Activity in Chronic Hepatitis C Patients2004

    • Author(s)
      Mochida S, Hashimoto M, Matsui A, Naito M, Inao M, Nagoshi S, Egashira T, Mishiro S, Fujiwara K
    • Journal Title

      Biochem Biophys Res Commun 313

      Pages: 1079-1085

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transgenic Mice Expressing Osteopontin in Hepatocytes as a Model of Autoimmune Hepatitis2004

    • Author(s)
      Mochida S, Yamamoto T, Mimura S, Matsui A, Ohno A, Koh H, Saitoh E, Nagoshi S, Fujiwara K
    • Journal Title

      Biochem Biophys Res Commun 317

      Pages: 114-120

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Imbalance of Th1 and Th2 Immune Reactions May Provoke Massive Liver Necrosis in Osteopontin Transgenic Mice2004

    • Author(s)
      Mimura S, Mochida S, Inao M, Matsui A, Nagoshi S, Yamamoto T
    • Journal Title

      J Gastroenterology 39

      Pages: 867-872

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Plasma Osteopontin Levels in Patients with Fulminant Hepatitis2004

    • Author(s)
      Matsui A, Mochida S, Ohno A, Nagoshi S, Hirose T, Fujiwara K
    • Journal Title

      Hepatology Res 22

      Pages: 202-206

    • NAID

      10018024812

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genetic Polymorphisms in Promoter Region of Osteopontin Gene May be a Marker Reflecting Hepatitis Activity in Chronic Hepatitis C Patients2004

    • Author(s)
      Mochida S, Hashimoto M, Matsui A, Naito M, et al.
    • Journal Title

      Biophysical and Biochemical Research Communications 313

      Pages: 1079-1085

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transgenic Mice Expressing Osteopontin in Hepatocytes as a Model of Autoimmune Hepatitis2004

    • Author(s)
      Mochida S, Yoshimoto T, Mimura S, Inao N, et al.
    • Journal Title

      Biophysical and Biochemical Research Communications 317

      Pages: 114-120

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Massive liver necrosis after provocation of imbalance between Th1 and Th2 immune reactions in osteopontin transgenic mice.2004

    • Author(s)
      Mimura S, Mochida S, Inao M, Matsui A, et al.
    • Journal Title

      Journal of Gastroenterology 39

      Pages: 867-872

    • NAID

      10013613344

    • Related Report
      2004 Annual Research Report
  • [Journal Article] SNPs in the Promoter Region of Osteopontin Gene as a Marker Predicting the Efficacy of Interferon-Based Therapies in Chronic Hepatitis C

    • Author(s)
      Naito M, Matsui A, Inao M, Nagoshi S, Nagano M, Ito N, Egashira T, Hashimoto M, Mishiro S, Mochida S, Fujiwara K
    • Journal Title

      J Gastroenterol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Extrahepatic manifestation in Transgenic Mice of Osteopontin in Hepatocytes : A Clue to Advent of Pathological State in Various Organs of Chronic Hepatitis C Patients

    • Author(s)
      Saitoh E, Matsui A, Inao M, Mimura S, Koh H, Ohno A, Nagoshi S, Kayano H, Yoshimoto T, Mochida S, Fujiwara K
    • Journal Title

      Hepatol Res (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Increased Cytoprotective Function in the Liver of Transgenic Mice Expressing Osteopontin in Hepatocytes

    • Author(s)
      Koh H, Matsui A, Mimura S, Inao M, Saitoh E, Ohno A, Nagoshi S, Yoshimoto T, Mochida S, Fujiwara K
    • Journal Title

      Hepatol Res (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 感染による病変の程度を予測するためのデータを収集する方法2003

    • Inventor(s)
      持田 智, 藤原 研司, 三代 俊治, 他
    • Industrial Property Rights Holder
      株式会社東芝
    • Filing Date
      2003-09-24
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 感染による病変の程度を予測するためのデータを収集する方法2003

    • Inventor(s)
      持田 智, 藤原 研司, 三代 俊治, 他
    • Industrial Property Rights Holder
      株式会社東芝
    • Filing Date
      2003-09-24
    • Related Report
      2004 Annual Research Report
  • [Publications] Mochida S, Yoshimoto T, Mimura S, Inao N, et al.: "Transgenic Mice Expressing Osteopontin in Hepatocytes as a Model of Autoimmune Hepatitis"Biophysical and Biochemical Research Communications. 317. 114-120 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mochida S, Hashimoto M, Matsui A, Naito M, et al.: "Genetic Polymorphisms in Promoter Region of Osteopontin Gene May be a Marker Reflecting Hepatitis Activity in Chronic Hepatitis C Patients"Biophysical and Biochemical Research Communications. 313. 1079-1085 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mimura S, Mochida S, Inao M, Matsui A, Nagoshi S, et al.: "Massive Liver Necrosis after Provocation of Imbalance between Th1 and Th2 Immune Reactions in Osteopontin Transgenic Mice"Journal of Gastroenterology. (印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kimura H, Mochida S, Inao M, Matsui A, Fujiwara K.: "Angiopoietib/Tie Receptors System may Play a Role During Reconstruction and Capillarization of the Hepatic Sinusoids after Partial Hepatectomy and Liver Injury in Rats"Hepatology Research. (印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsui A, Ohno A, Nagoshi S, Fujiwara K.: "Plasma Osteopontin Levels in Patients with Fulminant Hepatitis"Hepatology Research. (印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahashi M, Matsui A, Inao M, Mochida S, Fujiwara K.: "ERK/MAPK-depandent P13K/Akt phosphorylation through VEGFR-1 after VEGF stimulation in activated hepatic stellate cells"Hepatology Research. 26. 233-236 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujimori K, Mochida S, Matsui A, Ohno A, Fujiwara K.: "Possible mechanisms of evaluation of serum transaminase levels during interferon-beta therapy in chronic hepatitis C patients"Journal of Gastroenterology. 37. 40-46 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujiwara K, Mochida S.: "Indication and criteria for liver transplantation for fulminant hepatic failure"Journal of Gastroenterology. 37. 74-77 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyagawa Y, Imamura H, Soeda J, Matsunaga K, Mochida S, Fujiwara K, Matsuyama Y, Kawasaki K.: "Fate of hepatocytes and sinusoidal lining cell function and kinetics after extended cold preservation and transplantation of rat liver"Liver Transplantation. 8. 370-381 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi M, Matsui A, Inao M, Mochida S, Fujiwara K.: "ERK/MAPK-depandent PI3K/Akt phosphorylation through VEGFR-1 after VEGF stimulation in activated hepatic stellate cells"Hepatnlogy Research. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 藤原研司, 持田 智: "肝炎劇症化の機序<Editorial>"肝臓. 43. 341-351 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 持田 智, 藤原研司: "今月のテーマ「劇症肝炎,LOHFの現況」:我が国における劇症肝炎,LOHFの実態"日本消化器病学会誌. 99. 895-904 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujiwara K, Mochida S.: "Molecular Biology and Immunology in Hepatlogy : Advances in the Treatment of Intractable Liver Diseases"Tsuji T, et al. (eds), Elsevier, The Netherlamds. 275-284 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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