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

AMPA型谷氨酸受体运输系统候选基因分析

• 批准号: 17591237
• 负责人: HATTORI Eiji
• 金额: $ 2.24万
• 依托单位: RIKEN
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591237/
• 关键词: 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

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).

1.本项目的主要目的是研究AMPA型谷氨酸受体转运系统相关基因与精神分裂症和心境障碍的关系。我们研究的候选基因包括DLG 4（PSD-95）、DLG 1（SAP-97）、PRKCABP（PICK-1）、MDM 2。通过将计算机算法应用于从International HapMap Project下载的SNP数据来选择用于基因分型的SNP，以获得有效捕获感兴趣区域的基因组多样性的SNP集。在初步分析中，DLG 4基因的一个变异与精神分裂症显著相关。我们计划进行进一步的详细分析（传递不平衡检验、连锁不平衡分析和单倍型分析）。其他研究：1）编码微管相关蛋白之一的STOP基因在日本人群的病例对照样本中被发现与精神分裂症相关。还有，它的转录本在精神分裂症患者死后大脑的前额叶皮层中过度表达（Shimizu et al. 2006）。2）DRD 4基因上游的等位基因组合被认为会增加患精神分裂症的风险（Nakajima等，2006）。3）HTR 3B基因的单倍型显示与情绪障碍相关，特别是在女性亚组中（Yamada等人，2006年）。

项目成果

Association and synergistic interaction between promoter variants of the DRD4 gene in Japanese schizophrenics.

• DOI: 10.1007/s10038-006-0084-3
• 发表时间: 2007
• 期刊: JOURNAL OF HUMAN GENETICS
• 影响因子: 3.5
• 作者: Nakajima, Mizuho;Hattori, Eiji;Yamada, Kazuo;Iwayama, Yoshimi;Toyota, Tomoko;Iwata, Yasuhide;Tsuchiya, Kenji J.;Sugihara, Genichi;Hashimoto, Kenji;Watanabe, Hiroyuki;Iyo, Masaomi;Hoshika, Akinori;Yoshikawa, Takeo
• 通讯作者: Yoshikawa, Takeo

Association and synergic interaction between promoter variants of the DRD4 gene in Japanese schizophrenics

日本精神分裂症患者 DRD4 基因启动子变异之间的关联和协同相互作用

• 发表时间: 2006
• 期刊: J Hum Genet 52(1)
• 作者: Nakajim;Hattori et al.
• 通讯作者: Hattori et al.

Distinguishable Haplotype Blocks in the HTR3A and HTR3B Region in the Japanese Reveal Evidence of Association of HTR3B with Female Major Depression

• DOI: 10.1016/j.biopsych.2005.11.008
• 发表时间: 2006-07
• 期刊: Biological Psychiatry
• 影响因子: 10.6
• 作者: Kazuo Yamada;E. Hattori;Y. Iwayama;T. Ohnishi;Hisako Ohba;T. Toyota;Hitomi Takao;Y. Minabe;Noriaki Nakatani;T. Higuchi;S. Detera-Wadleigh;T. Yoshikawa

A promoter haplotype of the inositol monophosphatase 2 gene (IMPA2) at 18p11.2 confers a possible risk for bipolar disorder by enhancing transcription

• DOI: 10.1038/sj.npp.1301307
• 发表时间: 2007-08-01
• 期刊: NEUROPSYCHOPHARMACOLOGY
• 影响因子: 7.6
• 作者: Ohnishi, Tetsuo;Yamada, Kazuo;Yoshikawa, Takeo
• 通讯作者: Yoshikawa, Takeo

Genetic and expression analyses of the STOP (MAP6) gene in schizophrenia.

精神分裂症 STOP (MAP6) 基因的遗传和表达分析。

• 发表时间: 2006
• 期刊: Schizophrenia Research 84
• 作者: Tamagaki C;Sedvall GC;Jonsson EG;Okugawa G;Hall H;Pauli S;Agartz I;Nakajima M;Yamada K;Arai M;Iwayama Y;Yoshitsugu K;Shimizu H
• 通讯作者: Shimizu H