Disrupted Expression of Circadian Clock Genes in Patients with Bronchial Asthma

Circadian clock is synchronized to the 24-hour day by the daily light-dark cycle and proper function of circadian rhythm is essential for many physiological processes. Disruption of circadian rhythm can affect disease processes and influence disease severity, treatment responses, and even survivorship. In this retrospective case-controlled study, we tried to explore whether expression of circadian clock genes was disturbed in patients with bronchial asthma. We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes ( , , , , , , , , and ) in total leukocytes of peripheral blood collected at chest clinics from 120 patients with asthma and 60 health individuals. Expression levels of the nine circadian clock genes were significantly different between patients and healthy individuals, but not associated with the asthma control status. We also noted the difference of expression in asthmatic patients with and without nocturnal symptoms. In well-controlled asthmatics, expression of , , , , , and was significantly lower in patients with nocturnal symptoms than those without nocturnal symptoms. However, in not well-controlled asthmatics, expression of only , , , and was significantly different between patients with and without nocturnal symptoms. Binary logistic regression analysis selected , , , and as independent factors for bronchial asthma and ROC curves showed the combined expression of these four genes enhanced the capability of predicting asthma (AUC=0.924; 95% CI=0.875-0.958;