Project/Area Number |
13671034
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Psychiatric science
|
Research Institution | National Center of Neurology and Psychiatry (2002) Teikyo University (2001) |
Principal Investigator |
KUNUGI Hiroshi Head, Department of Mental Disorder Research, National Center of Neurology and Psychiatry, 疾病研究第三部, 部長 (40234471)
|
Co-Investigator(Kenkyū-buntansha) |
NANKO Shinichiro Professor, Department of Psychiatry, Teikyo University School of Medicine, 医学部, 教授 (60101127)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Keywords | 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) |
Research Abstract |
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.
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