| Project/Area Number |
16K09275
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General internal medicine(including psychosomatic medicine)
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
Ando Tetsuya 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 行動医学研究部, 室長 (50311428)
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| Co-Investigator(Kenkyū-buntansha) |
岡 晃 東海大学, 総合医学研究所, 講師 (80384866)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 摂食障害 / エクソーム解析 / 原因遺伝子 / 変異 / 罹患同胞 / エクソームシークエンシング / 家族症例 / ゲノム |
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| Outline of Final Research Achievements |
We performed whole-exome sequencing of 36 individuals in 10 families including eating disorder affected sib-pairs or a mother-daughter and extracted variants which were very rare (under 0.1%) in Japanese population, identical between patients in a family, not identical in healthy individuals, and estimated to be strongly deleterious by all 8 algorism. These investigations identified two variants as candidate factors of eating disorder. One was located in corticotropin releasing hormone receptor 2 (CRHR2) and the other was located in glutamate metabotropic receptor 8 (GRM8). Both were variants with non-synonymous substitution which altered the amino acid sequence of these proteins. Previous studies have also suggested that these genes are associated with psychiatric disorders. Therefore, we have successfully identified two genes that could be candidates for the etiology of eating disorders
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| Academic Significance and Societal Importance of the Research Achievements |
CRHR2はストレス応答時に視床下部から分泌されるホルモン CRHの受容体遺伝子である。CRHR2にCRHが結合すると脳下垂体からのACTH 分泌が刺激され、ACTHは副腎皮質からコルチゾールの分泌を促進する。コルチゾールは脳内で不安や食欲低下、交感神経の興奮に関係する。一方、CRHR2はCRHの作用のうち食欲抑制に関係する。GRM8は神経伝達物質のグルタミン酸の受容体遺伝子で脳で優勢に発現し、遺伝学的な解析により統合失調症、注意欠陥多動性障害、うつ病、摂食行動との関連が報告されてきた。いずれも摂食障害の候補遺伝子として期待され、今後は動物を用いた機能解析などさらに詳細な研究が必要である。
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