Analysis of association for single nucleotide polymorphism in OPRM1 with endocrine secretion and immune response in asthma

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09624
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Ohno Isao 東北医科薬科大学, 医学部, 教授 (00250762)
• Co-Investigator(Kenkyū-buntansha): 曽良 一郎 神戸大学, 医学研究科, 教授 (40322713)
• Project Period (FY): 2017-04-01 – 2021-03-31
• 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

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.

Free Research Field

呼吸器内科学

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。