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Screening for causative genes in unknown hemolytic anemia

Research Project

Project/Area Number 17591013
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionTokyo Women's Medical University

Principal Investigator

FUJII Hisaichi  Tokyo Woman's Medical University, School of Medicine, Professor, 医学部, 教授 (70107762)

Co-Investigator(Kenkyū-buntansha) KANNO Hitoshi  Tokyo Woman's Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (70221207)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsα-hemoglobin stabilizing protein / hemolytic anemia / acute hemolysis / single nucleotide polymorphisms (SNPs) / oxidative stress / antioxidant / 遺伝性非球状性溶血性貧血 / ピルビン酸キナーゼ異常症 / グルコース-6-リン酸脱水素酵素異常症 / 疾患感受性遺伝子
Research Abstract

Alpha-hemoglobin stabilizing protein (AHSP) binds specifically to α-hemoglobin, and prevents its precipitation in red blood cells (RBC). AHSP plays an important role as a molecular chaperone in the stabilization of unstable free α-globin monomer, which generates reactive oxygen species, resulting in damage to red cell protein and lipids. To examine that AHSP gene defects might account for either Heinz body-positive anemia or acute hemolytic anemia triggered by infection or drug administration, we performed a case-control study by examining seven SNPs (single nucleotide polymorphisms) of 28 hemolytic anemia patients and 95 controls, and found that a certain haplotype of the human AHSP gene had significant association with a subgroup of unknown hemolytic anemia. The haplotype included four SNPs (-557G,-465T,-201G and +248A) and a deletion-insertion polymorphism (DIP), T15, in 5'-flanking region of AHSP gene, and a reporter gene assay showed that the haplotype accounts for about 23% transcriptional activity of a control haplotype. In vitro mutagenesis analysis revealed that both the SNP-201G and T15 are responsible for decreased transcriptional activity of AHSP gene. We conclude that the AHSP gene is correlated to disease-susceptibility in a group of hemolytic anemia with either Heinz body-positive RBC or infection/drug-induced episodes, and that the homozygotes of-201A/T15 are more susceptible to oxidative stress.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (14 results)

All 2007 2006 2005

All Journal Article (12 results) Book (2 results)

  • [Journal Article] Transgenic rescue of hemolytic anemia due to red blood cell pyruvate kinase deficiency2007

    • Author(s)
      Hitoshi Kanno et al.
    • Journal Title

      Haematologica (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 寿命を終えた赤血球の処理機構~赤血球膜に出現する貪食目印分子に関する最近の知見~2007

    • Author(s)
      菅野 仁, 藤井 寿一
    • Journal Title

      Membrane 31・3(in press)

    • NAID

      130005077797

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Transgenic rescue of hemolytic anemia due to red blood cell pyruvatekinase deficiency2007

    • Author(s)
      Kanno H, et al.
    • Journal Title

      Haematologica (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 寿命を終えた赤血球の処理機構-赤血球膜に出現する貪食目印分子に関する最近の知見-2007

    • Author(s)
      菅野 仁, 藤井寿一
    • Journal Title

      Membrane 31・3(in press)

    • NAID

      130005077797

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 細胞療法・再生医療と中央部門のかかわり2006

    • Author(s)
      菅野 仁
    • Journal Title

      日本アフェレシス学会雑誌 25・3

      Pages: 226-232

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Biochemical and molecular basis of red blood cell pyrimidine5'-nucleotidase deficiency2006

    • Author(s)
      Hitoshi Kanno
    • Journal Title

      Genetic Errors Associated with Purine and Pyrimidine Metabolism in Humans : Diagnosis and Treatment

      Pages: 143-154

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ineffective erythropoiesis in mutant mice with deficient pyruvate kinase activity2005

    • Author(s)
      Shin Aizawa et al.
    • Journal Title

      Experimental Hematology 33・11

      Pages: 1292-1298

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A novel homozygous mutation of PKLR gene in a pyruvate-kinase-deficient Korean family2005

    • Author(s)
      Jeong Ok Park-Hah et al.
    • Journal Title

      Acta Haematologica 113・3

      Pages: 208-211

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ineffective erythropoiesis in mutant mice with deficient pyruvate kinase activity2005

    • Author(s)
      Shin Aizawa et al.
    • Journal Title

      Experimental Hematology 33(11)

      Pages: 1292-1298

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A novel homozygous mutation of PKLR gene in a pyruvate-kinase-deficient Korean family2005

    • Author(s)
      Jeong Ok Park-Hah et al.
    • Journal Title

      Acta Haematologica 113(3)

      Pages: 208-211

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ineffective erythropoiesis in mutant mice with deficient pyruvate kinase activity.2005

    • Author(s)
      Aizawa S, Harada T, Kanbe E, Tsuboi I, Aisaki K, Fujii H, Kanno H
    • Journal Title

      Exp.Hematol. 33(11)

      Pages: 1292-1298

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel homozygous mutation of PKLR gene in a pyruvate-kinase-deficient Korean family.2005

    • Author(s)
      Park-Hah JO, Kanno H, Kim WD, Fujii H
    • Journal Title

      Acta Haematol. 113(3)

      Pages: 208-211

    • Related Report
      2005 Annual Research Report
  • [Book] Genetic Errors Associated with Purine and Pyrimidine Metabolism in Humans : Diagnosis and Treatment2006

    • Author(s)
      Hitoshi Kanno
    • Publisher
      Biochemical and molecular basis of red blood cell pyrimidine 5'-nucleotidase deficiency
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Genetic errors associated with purine and pyrimidine metabolism in humans : diagnosis and treatment2006

    • Author(s)
      Kanno H
    • Total Pages
      196
    • Publisher
      Biochemical and molecular basis of red blood cell pyrimidine 5'-nucleotidase deficiency
    • Related Report
      2006 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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