Analysis of association for single nucleotide polymorphism in OPRM1 with endocrine secretion and immune response in asthma
| Project/Area Number |
17K09624
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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 |
Respiratory organ internal medicine
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
Ohno Isao 東北医科薬科大学, 医学部, 教授 (00250762)
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| Co-Investigator(Kenkyū-buntansha) |
曽良 一郎 神戸大学, 医学研究科, 教授 (40322713)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 気管支喘息 / μオピオイド受容体 / 遺伝子一塩基多型 / 精神的ストレス / 一塩基多型 / 遺伝子多型 / 増悪 / 呼吸器内科 / オピオイド |
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| Outline of Final Research Achievements |
Although population studies have implicated emotional burden in asthma severity, the underlying genetic risk factors are not completely understood. Using an ovalbumin-induced experimental asthma mouse model harboring the functionally equivalent SNP of OPRM1 A118G SNP (rs1799971), we investigated the mechanism by which this single-nucleotide polymorphism influences the allergic immune response. In comparison with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features and increased IL-4+CD4+ effector and effector memory T cells in the lungs under stressed conditions of everyday life. Blockade of peripheral mu-opioid receptors reduced the effector CD4+ T cell elevation associated with increased number of eosinophils in the bronchoalveolar lavage fluid of GG mice to the levels in AA mice, suggesting that elevated Th2 cell generation in the bronchial lymph node of GG mice is responsible for enhanced eosinophilic inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果から、μオピオイド受容体遺伝子の一塩基多型が、日常生活レベルのストレス下において、喘息免疫応答を亢進させ、喘息症状を悪化させている可能性が明らかとなった。加えて、リンパ組織に発現するμオピオイド受容体の遺伝子一塩基多型が喘息免疫応答の亢進に重要な役割を果たしている可能性が示唆された。本研究の成果は本邦における喘息患者個人の遺伝的要因（Genotype）に基づいた客観的かつ効果的なストレス誘発性喘息の予防や治療につながる基盤情報となる。
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Report
(5 results)
Research Products
(47 results)
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[Journal Article] The expression of 11 beta hydroxysteroid dehydrogenase in severe allergic rhinitis.2018
Author(s)
Ohta N, Noguchi N, Takahashi T, Suzuki T, Kakuta R, Suzuki Y, Awataguchi T, Suzuki T, Takahashi Y, Shoji F, Wada K, Kawano T, Ono I, Kusano Y, Miyasaka T, Osafune H, Matsutani S, Yaginuma Y, Ishida Y, Saito Y, Yamazaki M, Ikeda R.
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Journal Title
Otolaryngol Pol.
Volume: 73(2)
Issue: 5
Pages: 18-22
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 気管支喘息の増悪に関与する新たな危険因子：μオピオイド受容体遺伝子(OPRM1) の1塩基多型［SNP; A118G (rs1799971)］2020
Author(s)
宮坂智充, 川上佳織, 中村豊, 宮田敏, 佐藤美希, 目時弘仁, 曽良一郎, 山内広平, 河野資, 下川宏明, 高柳元明, 高橋知子, 大野勲.
Organizer
第54回 東北アレルギー懇話会
Related Report
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[Presentation] 気管支喘息増悪におけるTh2型免疫応答の亢進に関与するμオピオイド受容体一塩基多型2020
Author(s)
川上佳織, 宮坂智充, 中村豊, 宮田敏, 佐藤美希, 目時弘仁, 曽良一郎, 山内広平, 河野資, 下川宏明, 高柳元明, 高橋知子, 大野勲.
Organizer
アレルギー・好酸球研究会2020
Related Report
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[Presentation] The single nucleotide polymorphism (SNP) rs1799971 in the μ-opioid receptor gene (OPRM1) is a novel risk factor for asthma exacerbation.2020
Author(s)
Kaori Kawakami, Tomomitsu Miyasaka, Yutaka Nakamura, Satoshi Miyata, Miki Sato, Ichiro Sora, Hirohito Metoki, Kohei Yamauchi, Julie A. Blendy, Tasuku Kawano, Hiroaki Shimokawa, Tomoko Takahashi, Motoaki Takayanagi, Isao Ohno.
Organizer
JSA/WAO Joint Congress 2020.
Related Report
Int'l Joint Research
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