Investigation on candidate genes based upon the pathophysiological hypotothesis of schizophrenia

基于精神分裂症病理生理假说的候选基因研究

• 批准号: 18390323
• 负责人: ITOKAWA Masanari
• 金额: $ 11.12万
• 依托单位: Tokyo Metropolitan Organization for Medical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390323/
• 关键词: polymorphism; schizophrenia; case-control study; CDCV hypothesis; missense mutation; resequence; CDMRV hypothesis; linkage disequilibrium; トランスポーター; 連鎖不平衡(LD); 関連研究; グルタミン酸; ハプロタイプ

We performed case-control association study for VGLUT1/2 and ASCT1/2 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 Bonffeioni's correction.We resequenced DISC1 gene using 50 schizophrenia having affected relatives. We detected 32 novel mutations including 10 missense variants. These results supported common disease multiple rare variants hypothesis.

基于精神分裂症低谷氨酸能假说，我们对VGLUT1/2和ASCT1/2基因进行了病例对照关联研究。在VGLUT1基因区域检测到LD块，单倍型分析显示名义上显著相关（P=0.06）。IVS2+87A>G与偏执型精神分裂症有显著相关性（P = 0.01）。在VGLUT2基因区域检测到两个LD块，但单型频率在病例和对照组之间无显著差异。IVS2-49G>A与女性精神分裂症有显著相关性（P = 0.02）。经Bonffeioni校正后，这些关联并不显著。我们对50名患有精神分裂症的亲属进行了DISC1基因重测序。我们检测到32个新的突变，包括10个错义变体。这些结果支持常见病多罕见变异体假说。

项目成果

DISC1 antisense 鎖 DISC2について.

DISC1 反义链 关于 DISC2。

• 发表时间: 2006
• 作者: 新井誠;数藤由美子;Meerabux J;豊田倫子;大羽尚子;小幡菜々子;野原泉;大津嘉隆;柴田智行;古川愛造;吉川武男;糸川昌成.;松本英樹;永田 靖;福田正人;糸川昌成.
• 通讯作者: 糸川昌成.

Strategies to identify the genetic elements underlying schizophrenia.

识别精神分裂症遗传因素的策略。

• 发表时间: 2007
• 作者: Yoshikawa T;Suzuki-Aoki M;Yamada K;Hattori E;Toyota T;Iwayama Y;Itokawa M.
• 通讯作者: Itokawa M.

Novel scale including stiabismus and' cuspidal ear' for distinguishing schizophrenia patients from controls using minor physical anomalies.

新颖的量表包括斜视和“尖耳”，用于利用轻微的身体异常区分精神分裂症患者和对照组。

• 发表时间: 2006
• 期刊: Psychiatry Research 145(2-3)
• 作者: Yoshitsugu K;Yamada K;Toyota T;Aoki- Suzuki M;Minabe Y.;Nakamura K;Sekine Y;Suzuki K;Takei N;Itokawa M;Mori M;Yoshikawa T.
• 通讯作者: Yoshikawa T.

Association analysis of Sopioid receptor gene polymorphisms in methamphetamine dependence/psychosis.

甲基苯丙胺依赖/精神病中Sapioid受体基因多态性的关联分析。

• 发表时间: 2006
• 期刊: Am J Med Genet B Neuropsychiatr Genet. 141(5)
• 作者: Kobayashi H;Hata H;Ujike H;Harano M;Inada T;Komiyama T;Yamada M;Sekine Y;Iwata N;Iyo M;Ozaki N;Itokawa M. Naka M;Ide S;Ikeda K;Numachi Y.
• 通讯作者: Numachi Y.

統合失調症におけるASCT1の関連研究.

ASCT1在精神分裂症中的相关研究。

• 发表时间: 2007
• 作者: 小幡菜々子;野原泉;大津嘉隆;柴田智行;新井誠;羽賀誠一;古川愛造;吉川武男;糸川昌成.
• 通讯作者: 糸川昌成.