| Project/Area Number |
12470198
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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 | Saitama Medical School |
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Principal Investigator |
EBISAWA Takashi Saitama Medical School, Dept. of Psychiatry, Assistant Professor, 医学部, 講師 (00201369)
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| Co-Investigator(Kenkyū-buntansha) |
岩瀬 利郎 埼玉医科大学, 医学部, 助手 (80306307)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2001: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2000: ¥6,500,000 (Direct Cost: ¥6,500,000)
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| Keywords | delayed sleep phase syndrome / non-24-hour sleep-weak syndrome / clock-related genes / gene polymorphisms / system biology / 時計遺伝子 / カゼインキナーゼ / 概日リズム障害 / リン酸化 / メラトニン受容体 / G蛋白 / 季節性感情障害 / 危険因子 / 概日リズム / 睡眠覚醒リズム障害 / SSCP / period遺伝子 / Clock遺伝子 |
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| Research Abstract |
We are analyzing the genetic variations of clock genes in circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake syndrome (N-24). From melatonin 1a (Mella) and 1b (Mellb) receptor genes, a total of four missense variations were found. R54W variation in Mella receptor gene was observed in N-24 patients more frequently than in controls. When expressed in cultured cells with chimeric G-protein cDNAs, the R54W variant coupled with Gq protein less efficiently compared with wild-type Mella receptor. Missense variations in Mellb receptor were not likely to be related to the disorders. We have also found that [G647, P864, 4-repeat, T1037, R1158] haplotype of Per3 gene is significantly associated with DSPS. G647 is located close to the target residue for phosphorylation by casein kinase I epsilon (CK I ε), indicating that alteration in the PER3 phosphorylation may be involved in the increased disease susceptibility. T3111C polymorphism in CLOCK gene, which was reportedly associated with morningenss-eveningness seemed to be also involved in the development of DSPS. Analysis of the CK I ε gene was less in DSPS/N-24 than in controls, suggesting that the variation plays a protective role against the rhythm disorders. In vitro functional assay revealed that the CKI ε variant induces alteration of enzyme activity. These results indicate that multiple SNPs are involved in interindividual differences of human circadian rhythm and circadian rhythm sleep disorders are good precedents in establishing the analysis method for complex diseases.
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