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プロテオーム解析による統合失調症と双極性障害の病態に共通する分子の探索

Research Project

Project/Area Number 20659181
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Psychiatric science
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) 永井 拓  名古屋大学, 医学部附属病院, 准教授 (10377426)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2009: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2008: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywords統合失調症 / 双極性障害 / プロテオーム / タンパク発現 / 遺伝子翻訳後修飾
Research Abstract

リンパ芽球様細胞株は性別および年齢を一致させた統合失調症患者と対照健常者の末梢血液よりリンパ球細胞を単離し,エプスタイン・バールウイルスを用いて作成した.サンプルの調製は同一培養条件で21日間の継代培養を行った細胞からタンパク質を抽出した.2D-DIGE法を用いてタンパク質の発現差異解析を行い,PMF法により分子の同定を行った.さらに,同定されたタンパク質についてDAVIDを用いて同定分子の生体内における機能分類を行い,GSEAによって分類された項目の評価を行った.
性別および年齢の一致した統合失調症患者および健常者の末梢血液由来リンパ芽球様細胞株のうち,増殖の優れなかった細胞株は解析対象から除外し,患者・対照群それぞれ29例について2D-DIGE法によるタンパク質の網羅的発現差異解析を行った.各群において発現を認めた平均スポット数は,患者群1102.8±13.3個,対照群1102.6±16.2個であり,両群間に有意な差は認められなかった.検出された全1174個のスポットについて発現量を比較検討した結果,両群間において発現変化の認められたスポット数は20個であった(Student's t-test, p<0.05).発現変化の認められた20個のスポットについては,PMF法によるタンパク質の同定を行い,1つのスポットから複数のタンパク質の可能性が見出されたものを含め,22個のタンパク質を同定した.同定した22種類の分子についてDAVIDを用いて機能分類を行った.PANTHER Biological Processのデータベースに基づいてGSEAを行った結果,有意差の認められた項目は,"protein metabolism and modification"(7 genes), "ligand-mediated signaling"(5 genes), "apoptosis"(4 genes)であった。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (23 results)

All 2010 2009 2008

All Journal Article (20 results) (of which Peer Reviewed: 20 results) Presentation (3 results)

  • [Journal Article] Association study of bromodomain-containing 1 gene with schizophrenia in Japanese population.2010

    • Author(s)
      Kushima I, et al.
    • Journal Title

      Am J Med Genet B Neuropsychiatr Genet 153B(3)

      Pages: 786-91

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Novel Candidate Genes for Treatment Response to Risperidone and Susceptibility for Schizophrenia : Integrated Analysis Among Pharmacogenomics, Mouse Expression, and Genetic Case-Control Association Approaches.2010

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

      Biol Psychiatry 67(3)

      Pages: 263-9

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Copy Number Variation in Schizophrenia in the Japanese Population.2010

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

      Biol Psychiatry 67(3)

      Pages: 283-6

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic association study of KREMEN1 and DKK1 and schizophrenia in a Japanese population.2010

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

      Schizophr Res (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diagnostic classification of schizophrenia by neural network analysis of blood-based gene expression signatures.2010

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

      Schizophr Res (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain Cannabinoid CB2 Receptor in Schizophrenia.2010

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

      Biol Psychiatry 67(10)

      Pages: 974-982

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meta-analysis of association between genetic variants in COMT and schizophrenia : an update.2009

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

      Schizophr Res 110(1-3)

      Pages: 140-8

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association study of the G72 gene with schizophrenia in a Japanese population : a multicenter study.2009

    • Author(s)
      Ohi K, et al.
    • Journal Title

      Schizophr Res 109(1-3)

      Pages: 80-5

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia.2009

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

      Hum Mol Genet 18(13)

      Pages: 2483-94

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic analysis of the gene coding for DARPP-32 (PPP1R1B) in Japanese patients with schizophrenia or bipolar disorder.2008

    • Author(s)
      Yoshimi A, et al
    • Journal Title

      Schizophr Res 100(1-3)

      Pages: 334-341

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An association study of tachykinin receptor 3 gene with schizophrenia in the Japanese population.2008

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

      Neuroreport 19(4)

      Pages: 471-473

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] No association between prostate apoptosis response 4 gene (PAWR) in schizophrenia and mood disorders in a Japanese population.2008

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

      Am J Med Genet B Neuropsychiatr Genet 147B(4)

      Pages: 531-534

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between three serotonin receptor subtypes (HTR3A, HTR2A and HTR4) and treatment-resistant schizophrenia in the Japanese population.2008

    • Author(s)
      Ji X, et al
    • Journal Title

      Neurosci Lett 435(2)

      Pages: 95-98

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] No association between the protein tyrosine phosphatase, receptor-type, Z Polypeptide 1 (PTPRZl) gene and schizophrenia in the Japanese population.2008

    • Author(s)
      Ito Y, et al
    • Journal Title

      Am J Med Genet B Neuropsychiatr Genet 147B(7)

      Pages: 1013-1018

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A genetic association study of the FXYD domain containing ion transport regulator 6 (PXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population.2008

    • Author(s)
      Ito Y, et al
    • Journal Title

      Neurosci Lett 438(1)

      Pages: 70-75

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathway-based association analysis of genoine-wide screening data suggest that genes associated with the gamma-aminobutyric acid receptor signaling pathway are involved in neuroleptic-induced, treatment-resistant tardive dyskinesia.2008

    • Author(s)
      Inada T, et al
    • Journal Title

      Pharmacogenet Genomics 18(4)

      Pages: 317-323

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia.2008

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

      Pharmacogenomics 9(10)

      Pages: 1437-1443

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Failure to replicate the association between NRGI and schizophrenia using Japanese large sample.2008

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

      Schizophr Res 101(1-3)

      Pages: 1-8

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia.2008

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

      Hum Mol Genet 17(20)

      Pages: 3212-3222

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] No association between the oligodendrocyte-related gene PLP1 and schizophrenia in the Japanese population.2008

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

      J Hum Genet 53(9)

      Pages: 863-866

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] DISC1-interacting molecule and schizophrenia.2009

    • Author(s)
      Ozaki N.
    • Organizer
      9th World Congress of Biological Psychiatry : Symposium Genetic stratetegies in the search for genes in schizophrenia
    • Place of Presentation
      Paris, France
    • Year and Date
      2009-06-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] Glil-relaled gene and schizophrenia : Invited lecture2008

    • Author(s)
      Ozaki N
    • Organizer
      The Third Dual Congress on : "Psychiatry and the Neurosciences"
    • Place of Presentation
      Atens, Greece
    • Related Report
      2008 Annual Research Report
  • [Presentation] From ene to Phenotype in Schizophrenia- Invited lecture2008

    • Author(s)
      Ozaki N.
    • Organizer
      2nd WFSBP Asia-Pacific Congress
    • Place of Presentation
      富山
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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