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アストロサイト・オリゴデンドロサイト関連遺伝子を標的とした精神病性障害の病態研究

Research Project

Project/Area Number 18053011
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNagoya University

Principal Investigator

尾崎 紀夫  Nagoya University, 大学院・医学系研究科, 教授 (40281480)

Co-Investigator(Kenkyū-buntansha) 吉田 契造  名古屋大学, 医学部・附属病院, 講師 (60323151)
澤田 誠  名古屋大学, 環境医学研究所, 教授 (10187297)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2007: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywords統合失調症 / 双極性障害 / 覚醒剤使用障害 / アストロサイト / オリゴデンドロサイト / ゲノム
Research Abstract

統合失調症の病態にはシナプス連絡の障害が関与しており、その結果として認知機能障害が生じると考えられる。実際、シナプス連絡形成で中心的働きを果たすミエリン関連タンパクの異常が、統合失調症死後脳による網羅的発現解析で確認されている。さらに、白質病変の描出に優れるMRIのDTI画像所見でも統合失調症のミエリン異常が示唆されている。そこで、本年度はミエリン関連タンパク遺伝子である、SOX10,MOG, TF(transferring), CNP, OLIG2, ERBB3を候補遺伝子とし、統合失調症との関連解析を大規模ゲノムサンプル(患者768名および健常対照者768名)によって、倫理的配慮のもと実行した。その結果、SOX10のイントロン領域に存在するSNP、およびMOGの3'UTR領域に存在するVNTR多型と統合失調症との間に強い関連が見られた。TF、CNP、OLIG2、ERBB3の各遺伝子と統合失調症には関連は見られなかった。また、これまでCaucasianで強い関連が示唆されているCNPとOLIG2に関しては遺伝子-遺伝子相互作用を考慮した解析も実行したが、統合失調症との関連は見られなかった。今回の大規模遺伝子関連研究により日本人統合失調症患者の病態生理には欧米人種とは異なるミエリン関連タンパク遺伝子が関与していることが示唆された。現在、関連の見られた遺伝子多型の生理学的意義について、MRIによるDTIおよび認知機能を表現型として検討を行っている。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (29 results)

All 2007 2006

All Journal Article (24 results) (of which Peer Reviewed: 12 results) Presentation (5 results)

  • [Journal Article] Association study between Apolipoprotein L and schizophrenia by exhaustive and rule-based combination analysis for identification of multilocus interactions.2007

    • Author(s)
      Tomita Y, et. al.
    • Journal Title

      J Biosci Bioeng 103(4)

      Pages: 303-310

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of SOX10 with schizophrenia in the Japanese population.2007

    • Author(s)
      Maeno N, et. al.
    • Journal Title

      Psychiatr Genet 17(4)

      Pages: 227-231

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association study between the transferrin gene and schizophrenia in the Japanese population.2007

    • Author(s)
      Maeno N, et. al.
    • Journal Title

      Neuroreport 18(5)

      Pages: 517-520

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] No association between the glutamate decarboxylase 67 gene (GAD1) and schizophrenia in the Japanese population.2007

    • Author(s)
      Ikeda M, et. al.
    • Journal Title

      Schizophr Res 91(1-3)

      Pages: 22-26

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible association of beta-arrestin 2 gene with methamphetamine usedisorder, but not schizophrenia.2007

    • Author(s)
      Ikeda M, et. al.
    • Journal Title

      Genes Brain Behav 6(1)

      Pages: 107-112

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gap junction coding genes and schizophrenia: a genetic association study.2007

    • Author(s)
      Aleksic B, et. al.
    • Journal Title

      J Hum Genet 52(6)

      Pages: 498-501

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association Study between Vesicle-Associated Membrane Protein 2 Gene Polymorphisms and Fluvoxamine Response in Japanese Major Depressive Patients.2007

    • Author(s)
      Saito S, et. al.
    • Journal Title

      Neuropsychobiology 54(4)

      Pages: 226-230

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Promoter Haplotype of the Inositol Monophosphatase 2 Gene (IMPA2) at 18p11.2 Confers a Possible Risk for Bipolar Disorder by Enhancing Transcription.2007

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

      Neuropsychopharmacology 32(8)

      Pages: 1727-1737

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Functional Polymorphisms in the Promoter Region of the Human PICK1 Gene and Their Association With Methamphetamine Psychosis.2007

    • Author(s)
      Matsuzawa D, et. al.
    • Journal Title

      Am J Psychiatry 164(7)

      Pages: 1105-1114

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PICK1 is not a susceptibility gene for schizophrenia in a Japanese population: Association study in a large case-control population.2007

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

      Neurosci Res 58(2)

      Pages: 145-148

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Support for association of the PPP3CC gene with schizophrenia.2007

    • Author(s)
      Horiuchi Y, et. al.
    • Journal Title

      Mol Psychiatry 12(10)

      Pages: 891-893

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia.2007

    • Author(s)
      Hashimoto R, et. al.
    • Journal Title

      Mol Psychiatry 12(11)

      Pages: 1026-1032

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between chromogranin A gene Polymorphism and schizophrenia in the Japanese population2006

    • Author(s)
      Takahashi N. et al.
    • Journal Title

      Schizophr Res 83(2-3)

      Pages: 179-183

    • Related Report
      2006 Annual Research Report
  • [Journal Article] N : No association of complexin1 and complexin2 genes with schizophrenia in a Japanese population2006

    • Author(s)
      Kishi T. et al.
    • Journal Title

      Schizophr Res 82(2-3)

      Pages: 185-189

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The 2',3'-cyclic nucleotide 3'-phosphodiesterase and oligodendrocyte lineage transcription factor 2 genes do not appear to be associated with schizophrenia in the Japanese population2006

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

      Schizophr Res 88(1-3)

      Pages: 245-250

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association study of polymorphisms in the GluR7, KA1 and KA2 kainate receptor genes (GRIK3, GRIK4, GRIK5) with schizophrenia2006

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

      Psychiatry Res 141(1)

      Pages: 39-51

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Linkage disequilibrium and association with methamphetamine dependence/psychosis of mu-opioid receptor gene polymorphisms.2006

    • Author(s)
      Ise, et al.
    • Journal Title

      Pharmacogenomics J 6

      Pages: 179-188

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association of the Serotonin 5-HT(7) Receptor Gene with Schizophrenia in a Japanese Population.2006

    • Author(s)
      Ikeda M, et al.
    • Journal Title

      Neuropsychopharmacology 31(4)

      Pages: 866-871

    • Related Report
      2006 Annual Research Report
  • [Journal Article] No association of serotonin transporter gene (SLC6A4) with schizophrenia and bipolar disorder in Japanese patients : association analysis based on linkage disequilibrium2006

    • Author(s)
      Ikwda M, et al.
    • Journal Title

      J Neural Transm 113 (7)

      Pages: 899-905

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Positive association of AKT1 haplotype to Japanese methamphetamine use disorder.2006

    • Author(s)
      Ikeda M, et al.
    • Journal Title

      Int J Neuropsychopharmacol 9 (1)

      Pages: 77-81

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling2006

    • Author(s)
      Hashimoto R, et al.
    • Journal Title

      Hum Mol Genet 15 (20)

      Pages: 3024-3033

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association Study of the Dihydroyrimidinase-Related Protein 2 Gene and Methamphetamine Psychosis.2006

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

      Ann N Y Acad Sci 1074

      Pages: 90-96

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association analysis of delta-opioid receptor gene polymorphisms in methamphetamine dependence/psychosis2006

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

      Am J Med Genet B Neuropsychiatr Genet 14 (5)

      Pages: 482-486

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder2006

    • Author(s)
      Aoyama N, et al.
    • Journal Title

      Alcohol Clin Exp Res 30 (10)

      Pages: 1644-1649

    • Related Report
      2006 Annual Research Report
  • [Presentation] 精神障害に関与する遺伝因と環境因をどの様に患者・家族に伝えるべきか:精神科臨床における遺伝カウンセリング2007

    • Author(s)
      尾崎紀夫
    • Organizer
      第103回精神神経学会教育講演
    • Place of Presentation
      東京
    • Year and Date
      2007-11-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] Association study between the MPZL1/PZR gene and schizophrenia in the Japanese population.2007

    • Author(s)
      Usui H, et. al.
    • Organizer
      15th World Congress on Psychiatric Genetics
    • Place of Presentation
      New York, USA.
    • Related Report
      2007 Annual Research Report
  • [Presentation] Association study between the TACR3 gene polymorphisms and Japanese schizophrenia.2007

    • Author(s)
      Saito S, et. al.
    • Organizer
      15th World Congress on Psychiatric Genetics
    • Place of Presentation
      New York, USA.
    • Related Report
      2007 Annual Research Report
  • [Presentation] DISC1-interacting molecules and pathogenesis of schizophrenia: Candidate gene approach.2007

    • Author(s)
      Ozaki N, et. al.
    • Organizer
      2nd WFSBP International Congress of Biological Psychiatry: Symposium Pathogenesis of Schizophrenia
    • Place of Presentation
      Santiago, Chile.
    • Related Report
      2007 Annual Research Report
  • [Presentation] シンポジウム「疾患領域横断的遺伝学」統合失調症のゲノム解析:表現型同定とCDCV仮説の問題を中心に.2007

    • Author(s)
      尾崎紀夫
    • Organizer
      日本人類遺伝学会第52回大会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2018-03-28  

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