| Project/Area Number |
11670966
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Teikyo University |
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Principal Investigator |
KUNUGI Hiroshi Teikyo University School of Medicine, Lecturer, 医学部, 講師 (40234471)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Hidetoshi Teikyo University School of Medicine, Assistant, 医学部, 助手 (80328062)
NANKO Shinichiro Teikyo University School of Medicine, Professor, 医学部, 教授 (60101127)
李 圭博 帝京大学, 医学部, 助手 (40307202)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Schizophrenia / Neurodevelopment / Neueotrophic factor / Brain-derived neurotrophic factor / Glial cell derived neurotrophic factor / single nucleotide polymorphism / Hippocampus / Ventricular enlargement / 分子遺伝学 |
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| Research Abstract |
Several lines of evidence from neuroimaging and neuropathological studies have formulated schizophrenia as a neurodevelopmental disorder. Given the high heritability estimate of schizophrenia (>80%), genes which play an important role in neurodevelopment might be involved in the pathogenesis of the illness. We have examined the possible role of genes encoding neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial-cell derived neurotrophic factor (GDNF).
We searched for polymorphisms in the exonic region of the BDNF gene with polymerase chain reaction and single strand conformational polymorphism analysis. We detected a single nucleotide substitution (G758A) in the BDNF gene which results in an amino acid change (Val/Met). Then we examined this polymorphism for an association with schizophrenia in a Japanese sample of 316 patients with schizophrenia and 343 controls. There was no significant difference in the genotypic or allelic distribution between the two groups, suggesting that the G758A polymorphism has no major effect on the susceptibility to schizophrenia. Furthermore, we could not detect any significant effect of this polymorphism on ventricular-brain or hippocampus-brain ratio measured with MRI in a sample of 15 schizophrenics.
With regard to the GDNF gene, we examined the (AGG)n triplet repeat polymorphism in the 3' untranslated region for the possible role in the pathogenesis of schizophrenia. Although we did not find an unusually expanded allele, the 10-repeat allele (AGG)_<10> was significantly (p<0.05) more common in the schizophrenics (N=99) than in the controls (N=98), suggesting the possible relevance of the triplet repeat polymorphism to susceptibility to schizophrenia. Since the level of significance was not very high, further studies in larger sample sizes are required to conclude the possible involvement of this polymorphism in the pathogenesis of schizophrenia.
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