Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
Department of Human Pathology, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
Int J Mol Sci. 2023 Apr 19;24(8):7477. doi: 10.3390/ijms24087477.
The pathology of asthma is characterized by marked day-night variation, which is likely controlled by circadian clock activity. This study aimed to clarify the association of core circadian clock gene expression with clinical features of asthma. For this purpose, we accessed the National Center for Biotechnology Information database and analyzed transcriptomes of peripheral blood mononuclear cells and clinical characteristics of 134 pediatric/adolescent patients with asthma. Based on the expression patterns of seven core circadian clock genes (), we identified three circadian clusters (CCs) with distinct comorbidities and transcriptomic expressions. In the three CC subtypes, allergic rhinitis, and atopic dermatitis, both asthma comorbidities occurred in different proportions: CC1 had a high proportion of allergic rhinitis and atopic dermatitis; CC2 had a high proportion of atopic dermatitis but a low proportion of allergic rhinitis; and CC3 had a high proportion of allergic rhinitis but a low proportion of atopic dermatitis. This might be associated with the low activity of the FcεRI signaling pathway in CC2 and the cytokine-cytokine receptor interaction pathways in CC3. This is the first report to consider circadian clock gene expression in subcategories of patients with asthma and to explore their contribution to pathophysiology and comorbidity.
哮喘的病理学特征是明显的昼夜变化，这可能是由生物钟活动控制的。本研究旨在阐明核心生物钟基因表达与哮喘临床特征的关系。为此，我们访问了国家生物技术信息中心数据库，并分析了 134 名儿科/青少年哮喘患者的外周血单核细胞转录组和临床特征。基于七个核心生物钟基因（）的表达模式，我们确定了三个具有不同合并症和转录组表达的昼夜节律簇（CC）。在三个 CC 亚型中，过敏性鼻炎和特应性皮炎均以不同的比例发生哮喘合并症：CC1 具有高比例的过敏性鼻炎和特应性皮炎；CC2 具有高比例的特应性皮炎但低比例的过敏性鼻炎；CC3 具有高比例的过敏性鼻炎但低比例的特应性皮炎。这可能与 CC2 中 FcεRI 信号通路的低活性和 CC3 中细胞因子-细胞因子受体相互作用通路有关。这是首次考虑哮喘患者亚类中生物钟基因表达并探讨其对病理生理学和合并症的贡献的报告。
