| Project/Area Number |
07457207
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
TORU Michio Tokyo Medical and Dental Univ., School of Medicine, Dept. of Neuropsychiatry, Professor, 医学部, 教授 (20013972)
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| Co-Investigator(Kenkyū-buntansha) |
ARINAMI Tadao Univ. of Tsukuba, Institute of Basic Medical Sciences, Associate Professor,, 基礎医学系, 助教授 (10212648)
WATANABE Akiko Tokyo Medical and Dental Univ., School of Medicine, Dept. of Neuropsychiatry, Te, 医学部, 技官 (40210992)
KURUMAJI Akeo Tokyo Medical and Dental Univ., School of Medicine, Dept. of Neuropsychiatry, Le, 医学部, 助手 (00251504)
SHIBUYA Haruo Tokyo Medical and Dental Univ., School of Medicine, Dept. of Neuropsychiatry, As, 医学部, 助教授 (10158959)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | schizophrenia / affective disorder / alcohol dependence / dopamine D2 receptor gene / MTHFR gene variant / ドーパミンD1受容体 / ドーパミンD2受容体遺伝子 / アミノ酸ミスセンス変異 / ドーパミンD2受容体 |
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| Research Abstract |
Since the potency of antipsychotic drugs correlates with their affinity for the dopamine D2 receptor, this receptor gene might be a most possible caudidate gene for the pathoetiology of schizophrenics. Case-control studies in 419 schizophrenics, 78 patients with affective disorders, 393 patients with alcohol dependence and 579 control subjects on an association of several molecular variants mainly found in the dopamine D2 receptor. The frequency of schizophrenic patients with Cys311 variant was significantly higher particularly in whom without negatic symptoms (17%) when compared with the control (4%) (p<0.00001). This variant was found more frequently in patients with affective disorders with mood-incongruent psychotic features. (33%) (p<0.00001). We found Ins/Del polymorphism at -141C in the 5'region of DRD2 gene. The Del allele frequency was significantly lower in patients with schizophrenia than control subjects (OR : 0.6, p<0.001). Ala677Val polymorphism, which is responsible for the thermolabile methylenetetrahydrofolate reductase deficiency, was significantly more frequently observed in schizophrenic patients (OR : 1.9, p<0.0006).
We examined DRD2 gene polymorphism in patients with alcohol dependence. The patients carried Cys311 variant siguificantly more frequently than control (p<0.04). Alcoholic patients had -141 Ins Alle more frequently than controls (p<0.0005). We found that there were more frequent presence of Taq Ia1 allele in DRD2 gene in patients with alcohol dependence (p<0.006).
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