The A118G single-nucleotide polymorphism in OPRM1 is a risk factor for asthma severity
| Autor: | Kazuyoshi Kawakami, Kaori Kawakami, Hirohito Metoki, Julie A. Blendy, Kohei Yamauchi, Motoaki Takayanagi, Ichiro Sora, Tomoko Takahashi, Isao Ohno, Tasuku Kawano, Yutaka Nakamura, Miki Sato, Tomomitsu Miyasaka, Satoshi Miyata, Hiroaki Shimokawa |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Adult
Male OPRM1 T cell Population Receptors Opioid mu Allergic asthma Single-nucleotide polymorphism Polymorphism Single Nucleotide Severity of Illness Index Mice Th2 Cells Risk Factors Genotype medicine Animals Humans Immunology and Allergy SNP Polymorphism education A118G Asthma education.field_of_study Th2 cell differentiation business.industry Cell Differentiation General Medicine Middle Aged RC581-607 Eosinophil medicine.disease medicine.anatomical_structure Immunology Female Methacholine Immunologic diseases. Allergy business medicine.drug |
| Zdroj: | Allergology International, Vol 71, Iss 1, Pp 55-65 (2022) |
| ISSN: | 1323-8930 |
| DOI: | 10.1016/j.alit.2021.08.006 |
| Popis: | Background Although population studies have implicated emotional burden in asthma severity, the underlying genetic risk factors are not completely understood. We aimed to evaluate the genetic influence of a functional single-nucleotide polymorphism (SNP) in the stress-related μ-opioid receptor gene (OPRM1; A118G SNP, rs1799971) on asthma severity. Methods We initially assessed disease severity in asthmatic outpatients carrying A118G. Using an ovalbumin-induced experimental asthma rodent model harboring the functionally equivalent SNP, we investigated the mechanism by which this SNP influences the allergic immune response. Results Among 292 outpatients, 168 underwent airway hyperresponsiveness (AHR) to methacholine testing. Compared with patients carrying the AA and AG genotypes, those carrying the GG genotype exhibited enhanced AHR. The stress levels were presumed to be moderate among patients and were comparable among genotypes. Compared with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features and increased pulmonary interleukin-4+CD4+ effector and effector memory T cells under everyday life stress conditions. Intraperitoneal naloxone methiodide injection reduced effector CD4+ T cell elevation associated with increased eosinophil numbers in bronchoalveolar lavage fluid of GG mice to the levels in AA mice, suggesting that elevated Th2 cell generation in the bronchial lymph node (BLN) of GG mice induces enhanced eosinophilic inflammation. Conclusions Without forced stress exposure, patients with asthma carrying the OPRM1 GG genotype exhibit enhanced AHR, attributable to enhanced Th2 cell differentiation in the regional lymph node. Further research is necessary to elucidate the role of the OPRM1 A118G genotype in the Th2 cell differentiation pathway in the BLN. |
| Databáze: | OpenAIRE |
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