BMAL1–Sleep interactions modulate quality of life in allergic rhinitis patients with circadian dysregulation

Circadian CLOCK genes regulate sleep and circadian rhythms. Allergic rhinitis (AR) is frequently associated with sleep disturbances that can substantially impair patient quality of life (QoL). However, the relationship between circadian CLOCK gene expression in AR and sleep-related outcomes or QoL has not been established. This study included 133 participants (100 patients with AR and 33 healthy controls). Participants completed the Morningness-Eveningness Questionnaire (MEQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Pittsburgh Sleep Quality Index (PSQI). Circadian CLOCK gene expression in peripheral blood leukocytes was measured using qRT-PCR. The Mann-Whitney U test was used to compare the two independent groups and categorical variables were analyzed using the chi-square test. Linear regression evaluated the associations between circadian CLOCK gene expression and the RQLQ or sleep parameters. Patients with AR demonstrated significantly poorer sleep quality, longer sleep latency, more frequent nocturnal awakenings, and a higher prevalence of evening-type chronotypes along with dysregulated circadian gene expression in peripheral leukocytes compared to controls. Specifically, CLOCK and PER1 were upregulated and BMAL1 and CRY1 were downregulated. CLOCK expression was positively correlated with PSQI scores and negatively correlated with sleep duration in patients with AR, whereas PER2, CRY1, and CRY2 were positively correlated with sleep duration. BMAL1 expression was positively correlated with the total RQLQ score, activity limitations, and nasal symptoms. Furthermore, BMAL1 exhibited significant interactions with sleep duration on activity limitations and with sleep efficiency on nasal symptoms. Patients with AR exhibit circadian dysregulation, including imbalanced CLOCK genes, poor sleep, and evening chronotypes. The BMAL1-sleep interaction significantly influences the quality of life. Clinically, targeting this axis through interventions, such as sleep hygiene or chronotherapy, can enhance nasal symptoms and daily functioning beyond the benefits of conventional care.