| Project/Area Number |
16591128
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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 | University of Yamanashi |
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Principal Investigator |
SHIOE Kunihiko University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Assistant Professor, 大学院医学工学総合研究部, 講師 (90215939)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Masami University of Yamanashi, Health care Center, Associate Professor, 保健管理センター, 助教授 (80228808)
SHINOHARA Manabu University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, REsearch Associate, 大学院医学工学総合研究部, 助手 (30273048)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | bipolar disorder / mutation screening / polymorphism / TRPM2 / GRK3 / susceptible gene / 変異スクリーニング / SNP / 疾患感受性遺伝子 |
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| Research Abstract |
Several linkage analyses of bipolar disorder identified the potential susceptibility locus in chromosome region 21q22 and 22q12. TRPM2 (transient receptor potential melastatin 2) gene was identified on chromosome 21q22.3. The TRPM2 gene is expressed in various tissues, with the highest expression in brain. This protein is a calcium-permeable cation channel activated by ADP-ribose or reactive oxygen species. The GRK3 (G protein receptor kinase 3) gene maps to chromosome 22q12, and is expressed widely in brain. The GRK3 protein mediates homologous desensitization for a variety of neurotransmitters and hormones through phosphorylation of G protein-coupled receptors. The biological function, anatomical distribution, and chromosomal location of both TRPM2 and GRK3 gene led us prioritize it as the candidate genes of bipolar disorder. In this study, we analized in detail the promoter regions of both TRPM2 and GRK3 gene. Then, we performed association study of bipolar patients related to the promoter regions of the two genes. Screening of bipolar patients for mutations in the TRPM2 gene led to identification of one single nucleotide polymorphism (SNP) with a deletion and an insertion. Screening of the GRK3 gene revealed five novel and three known SNPs. In both TRPM2 and GRK3 gene, the comparison of the trasitions frequency in the bipolar patients (n=92) and controls (n=92) does not support the association of detected mutations with bipolar disorder.
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