Relationships between polymorphisms of genes encoding neurotrophic factors and neurodevelopment in schizophrenia

精神分裂症神经营养因子基因多态性与神经发育的关系

• 批准号: 09671008
• 负责人: KUNUGI Hiroshi
• 金额: $ 1.98万
• 依托单位: TEIKYO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671008/
• 关键词: Schizophrenia; Neurotrophic factor; Molecular genetics; Hippocampus; Neurodevelopment; Neurotrophin-3; Brain derived neurotrophic factor; ニューロトロフィン-3; 関連研究

Polymorphisms of gens encoding neurotrophic factors are possibly involved in the pathogenesis of schizophrenia. We searched for polymorphisms in the neurotrophin-3 (NT-3), brain derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) genes and explored their effects on susceptibility and neurodevelopmental abnormalities in schizophrenia.The Gly(-63)Glu polymorphism of the NT-3 gene was not significantly associated with susceptibility to schizophrenia when severity of the disease was not taken into account. A nucleotide substitution was found in the vicinity of the AP-1 binding site of the NT-3 gene ; however, it was not associated with susceptibility to schizophrenia. A dinucleotide repeat polymorphism of the NT-3 gene, which was previously reported to be associated with the risk of schizophrenia, was found to be associated with reduced volume of hippocampi in schizophrenic subjects, suggesting that this polymorphism may exert an effect on the development of schizophrenia through neurodevelopmental abnormalities of the CNS including hippocampus. We found two nucleotide substitutions in the promoter and 5 untranslated regions of the BDNF gene. These polymorphisms were suggested to be associated with the risk of developing schizophrenia. We could not find any polymorphism for the GDNF gene.Based on information from the Maternal and Child Health Handbook, we confirmed the prenatal underdevelopment in schizophrenia, including development of the eNS.However, there was no significant association of Gly(-63)Glu or the dinucleotide repeat polymorphism of the NT-3 gene with head circumference at birth of schizophrenics.

编码神经营养因子的基因多态性可能与精神分裂症的发病机制有关。我们寻找神经营养因子-3 （NT-3）、脑源性神经营养因子（BDNF）和神经胶质细胞系源性神经营养因子（GDNF）基因的多态性，并探讨它们对精神分裂症易感性和神经发育异常的影响。当不考虑疾病的严重程度时，NT-3基因的Gly(-63)Glu多态性与精神分裂症的易感性没有显著相关性。在NT-3基因的AP-1结合位点附近发现核苷酸替代；然而，它与精神分裂症的易感性无关。NT-3基因的二核苷酸重复多态性，先前被报道与精神分裂症的风险相关，被发现与精神分裂症受试者海马体积减少有关，这表明这种多态性可能通过包括海马在内的中枢神经系统神经发育异常对精神分裂症的发展产生影响。我们在BDNF基因的启动子和5个非翻译区发现了两个核苷酸替换。这些多态性被认为与患精神分裂症的风险有关。我们没有发现GDNF基因的多态性。根据《母婴健康手册》的信息，我们证实了精神分裂症患者的产前发育不足，包括ens的发育，但是，Gly(-63)Glu或NT-3基因的二核苷酸重复多态性与精神分裂症患者出生时的头围没有显著关联。

项目成果

Kunug:H 他: "Dinucleotide repest polymorphism in the newrotrophin-3 gene and hippocampal volune in psydroses." Schizophrenia Research. (印刷中). (1999)

Kunug：H 等人：“精神分裂症研究中 newrotropin-3 基因和海马体积的二核苷酸重复多态性”（出版中）。

Kunugi H 他: "Pinncleofide repeut polynorphism in the nemotrephin-3 gene and hippocanpol volume in psychoses" Schizophrenia Research. (印刷中). (1999)

Kunugi H 等人：“精神病中 Nemotrephin-3 基因和海马体积的 Pinncleofide 重复多态性”精神分裂症研究（1999 年出版）。

Kunugi H,Kato T,Fujii K,Hattori M,Kato N,Nanko S: "Dinucleotide repeat polymorphism in the neurotrophin-3 gene and hippocampal volume in psychoses." Schizophrenia Research. (in press).

Kunugi H、Kato T、Fujii K、Hattori M、Kato N、Nanko S：“神经营养素 3 基因中的二核苷酸重复多态性和精神病中的海马体积。”

Sasaki T,Doix Y,Kuwata S,et al.: "Brain-derived neurotrophic factor gene and schizophrenia in Japanese subjects." American Journal of Medical Genetics. 74巻. 443-444 (1997)

Sasaki T、Doix Y、Kuwata S 等人：“日本受试者的脑源性神经营养因子基因和精神分裂症”，《美国医学遗传学杂志》，第 74 卷，443-444（1997 年）。

Sakai T, Sasaki T,Tatsumi M et al.: "Schizophrenia and the ciliary neurotrophic factor(CNTF)gene:noevidence for association." Psychiatry Research. 71巻. 7-10 (1997)

Sakai T、Sasaki T、Tatsumi M 等人：“精神分裂症和睫状神经营养因子 (CNTF) 基因：没有证据表明存在关联。”精神病学研究第 71 卷，第 7-10 卷。