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Risk Factors for Asian Thrombophilia

Research Project

Project/Area Number 13576031
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Laboratory medicine
Research InstitutionKyushu University

Principal Investigator

HAMASAKI Naotaka  Graduate School of Medical Sciences Department of Clinical Chemistry and Laboratory Medicine Professor and Director, 医学研究院, 教授 (00091265)

Co-Investigator(Kenkyū-buntansha) MUTA Koichiro  Kyushu University Hospital Department of Internal Medicine Assistant Professor, 医学部附属病院, 助手 (50229928)
ISHIBASHI Tatsuro  Graduate School of Medical Sciences Department of Ophthalmology Professor and Director, 医学研究院, 教授 (30150428)
KANG Dongchon  Graduate School of Medical Sciences Department of Clinical Chemistry and Laboratory Medicine Associate Professor, 医学研究院, 助教授 (80214716)
古森 公浩  九州大学, 医学研究院, 助教授 (40225587)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2002: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2001: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordsthrombophilia / Prolein S / polymorphism / gene analysis / tertiary structure of protein S / 血栓症の病因解析 / ProteinC / ProteinS / 遺伝的背景
Research Abstract

Although the constitutional background of Japanese thrombotic patients has not been well examined, coagulation factor V Leiden is not detected in Japanese patients suffering from thromboses. We have been investigating constitutional predispositions of patients suffering from deep vein thrombosis in the Japanese population. In the present study, we summarize our results of Japanese patients suffering from deep vein thrombosis.
A surprisingly high frequency of Japanese patients suffering from deep vein thrombosis have reduced activity in the protein S/protein C anticoagulation system. Reduced activity in the protein S/protein C anticoagulation system was observed in 58% patients with deep vein thrombosis, while reduced activity of antithrombin was noted in 7% patients, a level consistent with the frequency in Caucasian patients. Gene analyses were performed on the factors associated with patients having reduced activities (10-12). Nineteen patients had mutated protein S genes, including 5 patients having protein S_<Tokushima>(K155E), 8 patients had mutated protein C genes, and two patients had mutated antithrombin genes.
Our study indicates that the frequency of inherited protein S abnormalities in Japanese patients suffering from deep vein thrombosis is significantly high, ten times higher than the frequency in Caucasian patients, and that abnormality of the protein S/protein C anticoagulation system is a major risk factor for deep vein thrombosis in Japan. It is interesting to note that the frequency of factor V Leiden in Caucasian deep vein thrombosis patients is similar to that of gene mutations of the protein S/protein C anticoagulalion system in Japanese deep vein thrombosis patients.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Tomomi Ide, Hiroyuki Tsutsui, Shunji, Naotaka Hamasaki, Akira Takeshita: "Mitochondrial DNA Damage and Dysfunction Associated with Oxidative Stress in Failing Hearts after Myocardial Infarction"Circ. Res.. 88. 529-535 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mutsuko Nakahara, Hiroko Iida, Michiyo Urata, Tsuneyoshi Yao, Naotaka Hamasaki: "A Novel Splice Acceptor Site Mutation of Protein S Gene in Affected Individuals with Type I Protein S Deficiency : Allelic Exclusion of the Mutant Gene"Throm. Res.. 101. 387-393 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroko Iida, Mutsuko Nakahara, Kimihiro Komori, Keizo Sugimachi, Naotaka Hamasaki: "Failure in the Detection of Aberrant mRNA from the Heterozygotic Splice Site Mutant Allele for Protein S in a Patient with Protein S Deficiency"Throm. Res.. 102. 187-196 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuda H, Urata M, Kinoshita S, Hamasaki N: "Four missense mutations identified in the protein S gene of thrombosis patients with protein S deficiency : Effects on secretion and anticoagulant activity of protein S"Thromb. Res.. 105. 233-239 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuda T, Tsuda H, Yoshimura H, Hamasaki N: "Dynamic Equilibrium between Protein S and C4b Binding Protein is Important for Accurate Determination of Free Protein S Antigen"Clin. Chem. Lab. Med.. 40. 563-567 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noki T, Young MT, Sakaguchi M, Hamasaki N, Tanner MJA: "The N-terminal region of the transmembrane domain of human erythrocyte band 3 : Residues critical for membrane insertion and transport activity"J. Biol. Chem.. 278(8). 5564-5573 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suematsu N, Tsutsui H, Wen J, Kang D, Ikeuchi M, Ide T, Hayashidani S, Shiomi T, Kubota T, Hamasaki N: "Oxidative Stress Mediates Tumor Necrosis Factor-alpha-Induced Mitochondrial DNA Damage and Dysfunction in Cardiac Myocytes"Circulation. 107. 1418-1423 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomomi Ide, Hiroyuki Tsutsui, Shunji, Naotaka, Hamasaki, Akira Takeshita: "Mitochondrial DNA Damage and Dysfunction Associated with Oxidative Stress in Failing Hearts after Myocardial Infarction"Circ. Res.. 88. 529-535 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mutsuko Nakahara, Hiroko Iida, Michiyo Urata, Tsuneyoshi Yao, Naotaka Hamasaki: "A Novel Splice Acceptor Site Mutation of Protein S Gene in Affected Individuals with Type I Protein S Deficiency: Allelic Exclusion of the Mutant Gene"Throm. Res.. 101. 387-393 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroko Iida, Mutsuko Nakahara, Kimihiro Komori, Keizo Sugimachi, Naotaka Hamasaki: "Failure in the Detection of Aberrant mRNA from the Heterozygotic Splice Site Mutant Allele for Protein S in a Patient with Protein S Deficiency"Throm. Res.. 102. 187-196 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiroko Tsuda, Michiyo Urata, Sachiko Kinoshita, Naotaka Hamasaki: "Four missense mutations identified in the protein S gene of thrombosis patients with protein S deficiency: Effects on secretion and anticoagulant activity of protein S"Throm. Res.. 105. 233-239 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomohide Tsuda, Hiroko Tsuda, Hajime Yoshimura, Naotaka Hamasaki: "Dynamic Equilibrium between Protein S and C4b Binding Protein is Important for Accurate Determination of Free Protein S Antigen"Clin. Chem. Lab. Med.. 40. 563-567 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanki T, Young MT, Sakaguchi M, Hamasaki N, Tanner MJA: "The N-terminal region of the transmembrane domain of human erythrocyte band 3: Residues critical for membrane insertion and transport activity"J. Biol. Chem.. 278(8). 5564-5573 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suematsu N, Tsutsui H, Wen J, Kang D, Ikeuchi M, Ide T, Hayashidani S, Shiomi T, Kubota T, Hamasaki N, Takeshita A: "Oxidative Stress Mediates Tumor Necrosis Factor-_-Induced Mitochondrial DNA Damage and Dysfunction in Cardiac Myocytes"Circulation. 107. 1418-1423 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomomi Ide, Hiroyuki Tsutsui, Shunji, Naotaka Hamasaki, Akira Takeshita: "Mitochondrial DNA Damage and Dysfunction Associated with Oxidative Stress in Failing Hearts after Myocardial Infarction"Circ. Res.. 88. 529-535 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mutsuko Nakahara, Hiroko Iida, Michiyo Urata, Tsuneyoshi Yao, Naotaka Hamasaki: "A Novel Splice Acceptor Site Mutation of Protein S Gene in Affected Individuals with Type I Protein S Deficiency : Allelic Exclusion of the Mutant Gene"Throm. Res.. 101. 387-393 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiroko Iida, Mutsuko Nakahara, KimihiroKomori, Keizo Sugimachi, Naokata Hamasaki: "Failure in the Detection of Aberrant mRNA from the Heterozygotic Splice Site Mutant Allele for Protein S in a Patient with Protein S Deficiency"Throm. Res.. 102. 187-196 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuda H, Urata M, Kinoshita S, Hamasaki N.: "Four missense mutations identified in the protein S gene of thrombosis patients with protein S deficiency : Effects on secretion and anticoagulant activity of protein S"Thromb. Res.. 105. 233-239 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuda T, Tsuda H, Yoshimura H, Hamasaki N.: "Dynamic Equilibrium between Protein S and C4b Binding Protein is Important for Accurate Determination of Free Protein S Antigen"Clin. Chem. Lab. Med.. 40. 563-567 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iida h.Ishi E, Nakahara M, Urata M, Wakiyama K, Kurihara M, Watanabe K, Kai T, Kinoshita S, Hamasaki N: "A Case of Congenital Afibrinogenemia : Fibrinogen Hakata, a Novel Nonsense Mutation of the Fibrinogen γ-Chain Gene"Thrombosis Haemostasis. 84(1). 49-53 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakahara M, Iida H, Urata M, Fujise M, Wakiyama M, Kinoshita S, Tsuda H, Okamura T, Yao K, Yao T, Hamasaki N: "A Novel Splice Acceptor Site Mutation of Protein S Gene in Affected Individuals with Type I Protein S Deficiency : Allelic Exclusion of the Mutant Gene"Thromosis Research. 101. 387-393 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iida h, Nakahara M, Komori K, Fujise M, Wakiyama M, Urata M, Kinoshita S, Tsuda H, Sugimachi K, Hamasaki N: "Failure in the Detection of Aberrant mRNA from the Heterozygotic Splice Site Mutant Allele for Protein S in a Patient with Protein S Deficiency"Thromosis Research. 102. 187-196 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Oka, T., Murata, Y., Namba, M., Yoshimizu, T., Takao Toyomura, T., Yamamoto, A., Ge-Hong Sun-Wada, Hamasaki, N., Wada, Y., Futai, M: "a4, a Unique Kidney-specific Isoform of Mouse Vacuolar H^+-ATPase Subunit α"J. Biological Chemistry. 276(43). 40050-40054 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Heinzmann A, (32 authers) Hamasaki N(28th): "Genetic variants of IL-13 signalling and human asthma and atopy"Human Molelcular Genetics. 9(4). 549-559 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ota K, Sakaguchi M, Hamasaki N, Mihara K.: "Membrane integration of the second transmembrane segment of band 3 requires closely apposed preceding signal-anchor sequence"J. Biological Chemistry. 275(38). 29743-29748 (2000)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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