Association of Circadian Clock Gene Expression with Pediatric/Adolescent Asthma and Its Comorbidities

Abstract

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 (CLOCK, BMAL1, PER1-3, CRY1-2), 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.

Keywords

• asthma
• circadian clock
• core clock genes
• comorbidity
• signaling pathways
• allergic rhinitis