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2005 Fiscal Year Final Research Report Summary

Investigation on candidate genes involved in pathophysiology of schizophrenia

Research Project

Project/Area Number 16390330
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionTokyo Institute of Psychiatry

Principal Investigator

ITOKAWA Masanari  Tokyo Institute of Psychiatry, Schizophrenia Research Project, Project Leader, 東京都精神医学総合研究所, 副参事研究員 (40332324)

Co-Investigator(Kenkyū-buntansha) IKEDA Kazuhiko  Tokyo Institute of Psychiatry, Acting President, 東京都精神医学総合研究所, 参事研究員 (30124663)
YOSHIKAWA Takeo  RIKEN, BSI, Lab., Molecular Psychiatry, Team Leader, チームリーダー (30249958)
Project Period (FY) 2004 – 2005
Keywordspolymorphism / schizophrenia / hypoglutamatergic hypothesis / case-control study / linkege disequillibrium / association study / GFAP / Reelin
Research Abstract

We performed case-control association study for VGLUT1/2 gene based upon the hypoglutamatergic hypothesis of schizophrenia. A LD block was detected in VGLUT1 gene region and haplotype analysis showed nominally significant association (P=0.06). IVS2+87A>G displayed significant association with paranoid type schizophrenia (P=0.01). Two LD blocks were detected in VGLUT2 gene region but haplytype frequencies showed no significant different between cases and controls. IVS2-49G>A was significantly associated with female schizophrenia (P=0.02). Those associations were not significant after Bonfferoni's correction.
Several lines of evidence support idea that functional disturbance of GFAP is involved in development of schizophrenia. We therefore investigated GFAP gene and 3 SNPs were significantly associated with schizophrenia (P<0.01). The data suggested that dysfunction of neuron-glia interaction could play a role in vulnerability of schizophrenia.
We detected positive association between Reelin gene and schizophrenia last year. SNPs which showed significant association could be related to splicing variations since they were located near intron/exon boundary. We performed RT-PCR for the exons of Reelin near the SNPs and detected novel spliced variant skipping exon9. Real-time PCR revealed mRNA skipping exon9 was elevated in schizophrenia compared to control brains.

  • Research Products

    (12 results)

All 2006 2005 Other

All Journal Article (12 results)

  • [Journal Article] Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia.2006

    • Author(s)
      Arai M, Yamada K, Toyota T, et a1.
    • Journal Title

      Biol. Psychiatry. 59

      Pages: 652-659

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A Polymorphism in the PDLIM5 Gene Associated with Gene Expression and Schizophrenia.2006

    • Author(s)
      Horiuchi Y, Arai M, Niizato K, et al.
    • Journal Title

      Biol Psychiatry. 59

      Pages: 434-439

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia2006

    • Author(s)
      Arai M, Yamada K, Toyota T, Obata N, Haga S, Yoshida Y, Nakamura K, Minabe Y, Ujike H, Sora I, Ikeda K, Mori N, Yoshikawa T, Itokawa M.
    • Journal Title

      Biol.Psychiatry. 59

      Pages: 652-659

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A Polymorphism in the PDLIM5 Gene Associated with Gene Expression and Schizophrenia.2006

    • Author(s)
      Horiuchi Y, Arai M, Niizato K, Iritani S, Noguchi E, Ohtsuki T, Koga M, Kato T, Itokawa M, Arinami T.
    • Journal Title

      Biol Psychiatry. 59

      Pages: 434-439

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A 200-kb region of human chromosome 22qllconfers schizophrenia-related behavioral abnormalities in mice.2005

    • Author(s)
      Hiroi N, Zhu H, Lee MS, et al.
    • Journal Title

      Proc Natl Acad Sci USA. 102

      Pages: 19132-19137

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genome-wide High-Density SNP Linkage Analysis of 236 Japanese Families Supports the Existence of Schizophrenia Susceptibility Loci on Chromosomes 1p, 14q, and 20p.2005

    • Author(s)
      Itokawa M.(51)
    • Journal Title

      Am. J. Hum. Genet. 77

      Pages: 937-944

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels.2005

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

      Biol Psychiatry. 57

      Pages: 1493-1503

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A 200-kb region of human chromosome 22q11 confers schizophrenia-related behavioral abnormalities in mice.2005

    • Author(s)
      Hiroi N, Zhu H, Lee MS, Funke B, Sawamura T, Arai M, Itokawa M, Kucherlapati R, Morrow B, Agatsuma S.
    • Journal Title

      Proc Natl Acad Sci USA. 102

      Pages: 19132-19137

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Japanese Schizophrenia Sib-Pair Linkage Group Genome-wide High-Density SNP Linkage Analysis of 236 Japanese Families Supports the Existence of Schizophrenia Susceptibility Loci on Chromosomes 1p, 14q, and 20p.2005

    • Author(s)
      Arinami T, Ohtsuki T, Ishiguro H, Ujike H, Tanaka Y, Morita Y, Mineta M, Takeichi M, Yamada S, Imamura A, Ohara K, Shibuya H, Ohara K, Suzuki Y, Muratake T, Kaneko N, Someya T, Inada T, Yoshikawa T, Toyota T, Yamada K, Kojima T, Takahashi S, Osamu O, Shinkai T, Nakamura M, Fukuzako H, Hashiguchi T, Niwa SI, Ueno T, Tachikawa H, Hori T, Asada T, Nanko S, Kunugi H, Hashimoto R, Ozaki N, Iwata N, Harano M, Arai H, Ohnuma T, Kusumi I, Koyama T, Yoneda H, Fukumaki Y, Shibata H, Kaneko S, Higuchi H, Yasui-Furukori N, Numachi Y, Itokawa M, Okazaki Y
    • Journal Title

      Am.J.Hum.Genet. 77

      Pages: 937-944

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels.2005

    • Author(s)
      Yamada K, Ohnishi T, Hashimoto K, Ohba H, Iwayama-Shigeno Y, Toyoshima M, Okuno A, Takao H, Toyota T, Minabe Y, Nakamura K, Shimizu E, Itokawa M, Mori N, Ito M, Yoshikawa T.
    • Journal Title

      Biol Psychiatry. 57

      Pages: 1493-1503

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Linkage disequilibrium and association with methamphetamine dependence/psychosis of mu-opioid receptor gene polymorphisms.

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

      Pharmacogenomics J. (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Linkage disequilibrium and association with methamphetamine dependence/psychosis of mu-opioid receptor gene polymorphisms.

    • Author(s)
      Ide S, Kobayashi H, Ujike H, Ozaki N, Sekine Y, Inada T, Harano M, Komiyama T, Yamada M, Iyo M, Iwata N, Tanaka K, Shen H, Iwahashi K, Itokawa M, Minami M, Satoh M, Ikeda K, Sora I.
    • Journal Title

      Pharmacogenomics J. (in press)

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

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Published: 2007-12-13  

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