Analysis of candidate genes in the AMPA-type glutamate receptor trafficking system

• Project/Area Number: 17591237
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: RIKEN
• Principal Investigator: HATTORI Eiji RIKEN, Laboratory for Molecular Psychiatry, Researcher, 分子精神科学研究チーム, 研究員 (80399443)
• Co-Investigator(Kenkyū-buntansha): IWAYAMA Yoshimi RIKEN, Laboratory for Molecular Psychiatry, Research Associate, 分子精神科学研究チーム, リサーチアソシエイト (60399441)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: genetics / genome / behavioral science / 候補遺伝子 / 統合失調症 / 双極性障害 / 関連研究 / 連鎖不平衡 / 病的代謝経路 / AMPA型受容体 / グルタミン酸神経伝達 / 精神疾患

Research Abstract

1. The major purpose of this project is to study on association of the genes involved in AMPA-type glutamate receptor trafficking system with Schizophrenia and mood disorders. We studied candidate genes including DLG4(PSD-95), DLG1(SAP-97), PRKCABP(PICK-1), MDM2. SNPs for genotyping were selected by applying a computer algorithm to the SNP data downloaded from the International HapMap Project to obtain a SNP set which efficiently captures the genomic diversity of the region of interest. In a preliminary analysis, a variant in the DLG4 gene was significantly associated with Schizophrenia. We are planning to conduct further detailed analyses (transmission-disequilibrium test, linkage disequilibrium analysis, and haplotypic analysis).
2. Other studies:
1) The STOP gene, which codes for one of the Microtubule-Associated-Proteins, was found to be associated with Schizophrenia in a case-control sample from a Japanese population. Also, its transcript was over-expressed in the prefrontal cortex of the Schizophrenia post-mortem brains (Shimizu et al. 2006).
2) An allelic combination of the upstream of the DRD4 gene was suggested to increase the risk for developing Schizophrenia (Nakajima et al. 2006).
3) A Haplotype of the HTR3B gene was shown to be associated with mood disorders particularly in the female subgroup (Yamada et al. 2006).

Research Products

• [Journal Article] Association and synergistic interaction between promoter variants of the DRD4 gene in Japanese schizophrenics. (2007)
  • Author(s): Nakajima M, Hattori E, Yamada K, Iwayama Y, Toyota T, Iwata Y, Tsuchiya KJ, Sugihara G, Hashimoto K, Watanabe H, Iyo M, Hoshika A, Yoshikawa T
  • Journal Title: J Hum Genet 52(1) Pages: 86-91
  • NAID: 10018515259
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Association and synergistic interaction between promoter variants of the DRD4 gene in Japanese schizophrenics. (2007)
  • Author(s): Nakajima M, Hattori E, Yamada K, Iwayama Y, Toyota T, Iwata Y, Tsuchiya KJ, Sugihara G, Hashimoto K, Watanabe H, Iyo M, Hoshika A, Yoshikawa T
  • Journal Title: J Hum Genet. 52(1)
  • NAID: 10018515259
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genetic and expression analyses of the STOP (MAP6) gene in schizophrenia (2006)
  • Author(s): Shimizu H, Iwayama Y, Yamada K, Toyota T, Minabe Y, Nakamura K, Nakajima M, Hattori E, Mori N, Osumi N, Yoshikawa T
  • Journal Title: Schizophr Res 84(2-3) Pages: 244-252
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression (2006)
  • Author(s): Yamada K, Hattori E, Iwayama Y, Ohnishi T, Ohba H, Toyota T, Takao H, Minabe Y, Nakatani N, Higuchi T, Detera-Wadleigh SD, Yoshikawa T
  • Journal Title: Biol Psychiatry 60(2) Pages: 192-201
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic and expression analyses of the STOP (MAP6) gene in schizophrenia (2006)
  • Author(s): Shimizu H, Iwayama Y, Yamada K, Toyota T, Minabe Y, Nakamura K, Nakajima M, Hattori E, Mori N, Osumi N, Yoshikawa T
  • Journal Title: Schizophr Res. 84(2-3) Pages: 244-252
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression (2006)
  • Author(s): Yamada K, Hattori E, Iwayama Y, Ohnishi T, Ohba H, Toyota T, Takao H, Minabe Y, Nakatani N, Higuchi T, Detera-Wadleigh SD, Yoshikawa T
  • Journal Title: Biol Psychiatry. 60(2) Pages: 192-201
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genetic and expression analyses of the STOP(MAP6) gene in schizophrenia (2006)
  • Author(s): Shimizu et al.
  • Journal Title: Schizopr Res 84(2-3) Pages: 244-252
• [Journal Article] Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder : relevance to neuronal network perturbation (2006)
  • Author(s): Nakatani, Hattori et al.
  • Journal Title: Hum Mol Genet 15(12) Pages: 1949-1962
• [Journal Article] Association and synergic interaction between promoter variants of the DRD4 gene in Japanese schizophrenics (2006)
  • Author(s): Nakajim, Hattori et al.
  • Journal Title: J Hum Genet 52(1) Pages: 86-91
• [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.
  • Author(s): Ohnishi et al.
  • Journal Title: Neuropsychopharmacology (in press)
• [Journal Article] Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression
  • Author(s): Yamada et al.
  • Journal Title: Biol.Psychiatry (印刷中)