| Project/Area Number |
15591249
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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 | Shinshu University |
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Principal Investigator |
WASHIZUKA Shinsuke Shinshu University, Center for Health, Safety, and Environmental Management, Associate professor, 健康安全センター, 教授 (60313855)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Tadafumi RIKEN Brain Science Institute, Laboratory for Molecular Dynamics of Mental Disorders, Laboratory Head, 脳科学総合研究センター, チームリーダー (30214381)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | bipolar disorder / mitochondria / polymorphism / gene expression / promoter assay / mood stabilizer / treatment / NDUFV2 / 双極性障害 |
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| Research Abstract |
Several studies have suggested mitochondrial abnormality in bipolar disorder (BD). We previously reported the association of mitochondrial DNA (mtDNA) 5178 and 10398 polymorphisms with BD. We examined the association of these polymorphisms with some clinical variables in 54 bipolar patients. Our study revealed that patients carrying the 10398A polymorphism showed a significantly better response to lithium. Both these polymorphisms cause amino acid substitution in subunits of the mitochondrial complex I. Most subunits of complex I are coded in the nuclear genome. Of those, NDUFV2 is located at 18p 11, the locus reported to be linked with BD. We previously reported that a polymorphism, -602G>A, was significantly associated with BD. We further screened the upstream region of this gene. We found that the haplotype blocks surrounding -602G>A and -3542G>A were associated with BD. The association of the haplotypes consisting of these 2 polymorphisms with BD was seen both in Japanese case-control samples and NIMH trios. Furthermore the -602G>A polymorphism was found to alter the promoter activity. Decreased gene expression in patients with bipolar I disorder compared with controls was found in most of the nuclear encoded complex I subunit genes. In addition, decreased expression levels of these genes were marginal compared with the marked decrease of the NDUFV2, but correlated with that of NDUFV2 gene. Together these findings indicate that the polymorphisms in the promoter region of NDUFV2 are genetic risk factor for BD, and the decreased expression of NDUFV2 has a considerable effect on other subunit genes in the mitochondrial respiratory chain.
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