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

Yang Yang,Hung Hung,Lin Lin,Friedman Friedman,Salapatas Salapatas,Chen Chen

doi:10.3390/jcm8101634

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.

Highlights

Obstructive sleep apnea/hypopnea (OSA) syndrome is characterized by repetitive obstruction of the upper airway and causes repetitive hypoxia/reoxygenation
Circadian rhythm refers to the “body clock” which is an endogenously driven, nearly 24-hour cycle in biochemistry, physiology, or behavior, such as sleep and activity, appetite, hormone levels, metabolism, and gene expression [6]
It is accepted that peripheral blood (PB) cells contain a circadian clock similar to that in the suprachiasmatic nucleus [7]

Summary

Introduction

Obstructive sleep apnea/hypopnea (OSA) syndrome is characterized by repetitive obstruction of the upper airway and causes repetitive hypoxia/reoxygenation. Circadian rhythm refers to the “body clock” which is an endogenously driven, nearly 24-hour cycle in biochemistry, physiology, or behavior, such as sleep and activity, appetite, hormone levels, metabolism, and gene expression [6]. It is accepted that peripheral blood (PB) cells contain a circadian clock similar to that in the suprachiasmatic nucleus [7]. Circadian rhythms are ubiquitous phenomena, and are found, for example, in the sleep-wake cycle, body-core temperature, leukocyte count, trace metal concentrations, and levels of many hormones, such as cortisol and melatonin [9,10]. A stable human biological clock helps to regulate sleep patterns, hormone release, and blood pressure, etc. Serious adverse events including cancers, atherosclerosis, myocardial infarction, and stroke are significantly associated with the disturbance of circadian gene expressions [9]

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