Alternations of Circadian Clock Genes Expression and Oscillation in Obstructive Sleep Apnea

Abstract

Circadian misalignment plays an important role in disease processes and can affect disease severity, treatment outcomes, and even survivorship. In this study, we aim to investigate whether expression and daily oscillation patterns of core circadian clock genes were disturbed in patients with obstructive sleep apnea/hypopnea (OSA) syndrome. We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes in leukocytes of peripheral blood collected at 12 AM, 6 AM, 12 PM, and 6 PM from 133 patients with OSA and 11 normal controls. Daily expression patterns of the nine circadian clock genes were observed in normal controls, but three of these genes (BMAL1, CLOCK, CRY2) were disrupted in patients with OSA. The expressions of eight circadian clock genes (except PER1) at midnight were significantly downregulated in patients with severe OSA. Binary logistic regression analysis selected CRY1 and PER3 as independent factors for severe OSA and showed that the combined expressions of CRY1 and PER3 enhanced the capability of predicting severe OSA (Odds ratio, 5.800; 95% CI, 1.978 to 17.004; p = 0.001). Our results show that combined expressions of CRY1 and PER3 at midnight could be a potential predictor for severe OSA.

Effect of Type 2 Diabetes Mellitus on the Hypoxia-Inducible Factor 1-Alpha Expression. Is There a Relationship with the Clock Genes?

“…Whether these metabolic disruptions are perpetuated by chronic hyperglycemia or sleep breathing disorders remains to be elucidated. Similarly, the combined downregulation in the expressions of CRY1 and PER3 at midnight predicted the severity of the disease in patients with obstructive sleep apnea/hypopnea syndrome [18]. Additionally, in patients with type 2 diabetes, those with the poorest sleep quality showed a dampened mRNA expression of clock genes such as BMAL1 and PER1 [33].…”

“…Until now, there have been limited reports on the relationships between regulation of oxygen homeostasis and circadian clock genes in type 2 diabetes [18,19]. To further increase our knowledge in this emerging field, we have designed a study to examine whether the expression of HIF-α subunits (HIF-1α and HIF-2α) is connected with changes in the expression of eight core circadian clock genes according to the presence of type 2 diabetes.…”

Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease

“…Although there is limited data on the role of the circadian clock in OSA ( von Allmen et al, 2018 ; Yang et al, 2019 ; Gabryelska et al, 2020 ), it may play a significant role in this disease ( Entzian et al, 1996 ; Smith et al, 2017 ; Butler et al, 2015 ). We found dysregulation of circadian gene expression in multiple cell types.…”

Altered Expression of Circadian Clock Genes in Patients with Atrial Fibrillation Is Associated with Atrial High-Rate Episodes and Left Atrial Remodeling

“…Sleep disorder was associated with a higher AF recurrence rate in patients receiving either medication or ablation therapy [ 16 ]. Additionally, sleep disorder will cause alternations in circadian clock genes expression and oscillation [ 17 ]. Our previous study found that sleep disorders can affect the performance of physiological clock genes of PB total leukocytes, and cause disease, such as sudden deafness [ 13 ].…”