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2004 Fiscal Year Final Research Report Summary

Analysis of possible association between α-tocopherol transfer protein gene and diabetes mellitus or its clinical complications.

Research Project

Project/Area Number 15590956
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionThe University of Tokyo (2004)
Tokyo Women's Medical University (2003)

Principal Investigator

GOTODA Takanari  The University of Tokyo, Faculty of Medicine, Visiting Associate Professor, 医学部附属病院, 客員助教授 (60322062)

Co-Investigator(Kenkyū-buntansha) KUSAKA Takako  Tokyo Women's Medical University, Faculty of Medicine, Assistant, 医学部, 助手 (20338974)
Project Period (FY) 2003 – 2004
Keywordsvitamine E / diabetes / complication
Research Abstract

We found that serum levels of α-and γ-tocopherol were significantly decreased in patients with diabetes mellitus as compared with non-diabetic subjects. A C-to-T polymorphism in intron 4 of the human α-tocopherol transfer protein (α-TTP) gene has been shown to be associated with serum tocopherol levels (T-allele associated with lower levels). We further screened the human α-TTP gene for gene mutation or gene variant, and identified a variable number (9〜12) of adenine nucleotide repeat located 335 nucleotides upstream of the putative transcription initiation site. The allelic frequency of the -335A(n) polymorphism was as follows ; A(10)>A(11)>>A(9), A(10). Both the intron 4 C/T polymorphism and the -335A(n) polymorphism were almost in tight linkage disequilibrium, with the T-allele linked to the A(11)-allele. Luciferase promoter assay in 293 cells revealed that the reporter construct containing the A(11)-allele had significantly lower promoter activity than that containing the A(10)-allele. Among diabetic patients, the T-allele, and therefore the A(11)-allele as well, have been shown to be associated with occurrence of diabetic retinopathy [OR=1.76 (95%CI : 1.03-2.89). These results encourage further investigation about possible association between α-TTP and diabetic complications.

  • Research Products

    (10 results)

All 2004 2003

All Journal Article (10 results)

  • [Journal Article] Mutations in Japanese subjects with primary hyperlipidemia.2004

    • Author(s)
      Maruyama T, Gotoda T. et al.
    • Journal Title

      J Atheroscler Thromb 11

      Pages: 131-145

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] p53 involvement in the pathogenesis of fatty liver.2004

    • Author(s)
      N.Yahagi, T.Gotoda, et al.
    • Journal Title

      J.Biol Chem 279

      Pages: 20571-20575

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] p53 involvement in the pathogenesis of fatty liver disease.2004

    • Author(s)
      Yahagi N., Gotoda T., et al.
    • Journal Title

      J.Biol.Chem 279

      Pages: 20571-20575

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mutations in Japanese subjects with primary hyperlipidemia.2004

    • Author(s)
      Maruyama T, Gotoda T., et al.
    • Journal Title

      J Atheroscler Thromb 11

      Pages: 131-145

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Binge eating as a phenotype of melanocortin4 receptor gene mutations.2003

    • Author(s)
      T.Gotoda
    • Journal Title

      N Engl J Med 349

      Pages: 606-606

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Early embryonic lethality caused by targeted disruption of the 3-hydroxy-3-methylglutaryl CoA reductase gene.2003

    • Author(s)
      K.Ohashi, T.Gotoda, et al.
    • Journal Title

      J Biol Chem 278

      Pages: 42936-42941

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus.2003

    • Author(s)
      T.Yokoo, T.Gotoda, et al.
    • Journal Title

      J Biol Chem 278

      Pages: 52919-52923

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Binge eating as a phenotype of melanocortin 4 receptor gene mutations.2003

    • Author(s)
      Gotoda T
    • Journal Title

      N.Engl.J.Med. 349

      Pages: 606

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Early embryonic lethality caused by targeted disruption of the 3-hydroxy-3-methylglutaryl-CoA reductase gene.2003

    • Author(s)
      Ohashi K., Gotoda T., et al.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 42936-42941

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus.2003

    • Author(s)
      Yokoo T., Gotoda T., et al.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 52919-52923

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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