Polymorphism screening and association analysis of neurotrophic factor genes in neuropsychiatric diseases

神经精神疾病神经营养因子基因多态性筛选及关联分析

• 批准号: 13671034
• 负责人: KUNUGI Hiroshi
• 金额: $ 2.5万
• 依托单位: National Center of Neurology and Psychiatry (2002)Teikyo University (2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671034/
• 关键词: neurotrophic factor; VGF; p75; neurotrophin-3; schizophrenia; Alzheimer's disease; polymorphism; association study; ニューロトロフィン-3; 精神分裂病; 一塩基多型(SNP)

Based on the neurodevelopmental hypothesis in the etiology of schizophrenia, neurotrophic factors (NTFs) maybe involved in the pathogenesis of the illness. NTFs are also implicated in the pathogenesis of neurodegenerative diseases. We searched for polymorphisms for genes encoding brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), their low affinity receptor p75, and vgf, which is induced by neurotrophins during development and differentiation of the central nervous system. Detected polymorphisms were subject to association analyses with neuropsychiatric diseases. We found that a particular haplotype (G[[-3004]-A3] in the NT-3 gene was significantly associated with schizophrenia (p=0.005), suggesting that this haplotype gives susceptibility to schizophrenia. Using direct sequencing, we found two single nucleotide polymorphisms (SNPs) in the p75 gene, one of which results in an amino-acid change. When this polymorphism was examined for the possible association with schizophrenia and Alzheimer's disease, however, there was no significant difference in the genotype or allele distribution between patients and controls. With respect to the vgf gene, we found several differential sequences from those sequences that were previously published. However, we obtained no evidence for the presence of polymorphisms in our sample, suggesting that DNA sequence of the vgf gene is highly conserved. Further investigations on the possible role of the NT-3 gene in the pathogenesis of schizophrenia are warranted.

基于精神分裂症病因学中的神经发育假说，神经营养因子可能参与了精神分裂症的发病机制。NTFs也与神经退行性疾病的发病机制有关。我们寻找了编码脑源性神经营养因子（BDNF）、神经营养因子-3 （NT-3）、它们的低亲和力受体p75和vgf的基因多态性，vgf是在中枢神经系统发育和分化过程中由神经营养因子诱导的。检测到的多态性将与神经精神疾病进行关联分析。我们发现NT-3基因中一种特定的单倍型（G[[-3004]-A3]）与精神分裂症显著相关（p=0.005），这表明这种单倍型导致精神分裂症易感性。通过直接测序，我们在p75基因中发现了两个单核苷酸多态性（SNPs），其中一个导致氨基酸变化。然而，当检查这种多态性与精神分裂症和阿尔茨海默病的可能关联时，患者和对照组之间的基因型或等位基因分布没有显着差异。关于vgf基因，我们从之前发表的那些序列中发现了几个差异序列。然而，我们在样本中没有获得多态性存在的证据，这表明vgf基因的DNA序列是高度保守的。NT-3基因在精神分裂症发病机制中的可能作用有待进一步研究。

项目成果

Kunugi H. 他: "Brain derived neurotrophic factor gene and schizophrenia : polymorphism screening and association analysis"Schizopjr. Res.. (印刷中).

Kunugi H.等人：“脑源性神经营养因子基因与精神分裂症：多态性筛选和关联分析”Schizopjr..（正在出版）。

Kunugi H, Akahane A, Tanaka H, Nanko S: "Polymorphism analysis on the vgf gene in neuropsychiatric diseases"Annual Report of Pharmacopsychiatry Research. 34. 29-33 (2002)

Kunugi H、Akahane A、Tanaka H、Nanko S：“神经精神疾病中 vgf 基因的多态性分析”药物精神病学研究年度报告。

Hattori M ほか: "Novel polymorphisms in the promoter region of the neurotrophin-3 gene and their associations with schizophrenia"American Journal of Medical Genetics. 114. 304-309 (2002)

Hattori M 等人：“神经营养素 3 基因启动子区域的新多态性及其与精神分裂症的关联”美国医学遗传学杂志 114. 304-309 (2002)。

Hattori M, Kunugi H, Akahane A, Tanaka H, Ishida S, Hirose T, Morita R, Yamakawa K, Nanko S: "Novel polymorphisms in the promoter region of the neurotrophin-3 gene and their associations with schizophrenia"American Journal of Medical Genetics. 114 (3). 30

Hattori M、Kunugi H、Akahane A、Tanaka H、Ishida S、Hirose T、Morita R、Yamakawa K、Nanko S：“神经营养素 3 基因启动子区的新多态性及其与精神分裂症的关系”美国医学杂志

功刀 浩 ほか: "神経栄養因子遺伝子と精神神経疾患:VGF遺伝子の変異解析"精神薬療研究年報. 34. 29-33 (2002)

Hiroshi Kuto 等：“神经营养因子基因和神经精神疾病：VGF 基因的突变分析”精神药理学治疗研究年度报告。 34. 29-33 (2002)。