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Clock gene dysfunction in patients with obstructive sleep apnoea syndrome

¹ Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, and ² Pharmaceutics, Division of Clinical Pharmacy, Dept of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan, ³ Both authors contributed equally to the study.

CORRESPONDENCE: N. Burioka, Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1 Nishimachi, Yonago 683-8504, Japan. Fax: 81 859386539. E-mail: burioka{at}grape.med.tottori-u.ac.jp

Keywords: Clock gene, C-reactive protein, interleukin-6, noradrenaline, Period1, sleep apnoea

Received: October 19, 2007
Accepted February 11, 2008

Clock genes regulate mammalian circadian rhythms, and dysfunction of clock genes can contribute to various disorders. To investigate whether obstructive sleep apnoea syndrome (OSAS) influences clock gene function, the present authors examined Period1 (Per1) mRNA expression in vitro and in vivo.

In eight healthy subjects and eight OSAS patients, plasma noradrenaline, serum interleukin (IL)-6, high-sensitivity C-reactive protein (hsCRP) and Per1 mRNA expression in peripheral whole blood were measured. Expression of Per1 mRNA in cultured cells was examined under IL-6 or noradrenaline stimulation in vitro. After noradrenaline was administered to mice in vivo, Per1 mRNA expression in the brain was examined.

The concentrations of serum IL-6, hsCRP and plasma noradrenaline were elevated in OSAS patients, but improved by continuous positive airway pressure (CPAP) therapy. Per1 mRNA expression in the peripheral blood significantly decreased at 02:00 h by CPAP in OSAS patients. Stimulation with IL-6 did not directly induce Per1 mRNA in vitro. Administration of noradrenaline induced Per1 mRNA in the cerebral cortex of mice in vivo.

The current study revealed that obstructive sleep apnoea syndrome caused clock gene dysfunction, and continuous positive airway pressure helped to improve it. Sympathetic activation and elevation of the plasma noradrenaline concentration in obstructive sleep apnoea syndrome may be one of the factors involved in disorders of Period1 mRNA expression.