Clock gene dysfunction in patients with obstructive sleep apnoea syndrome

¹ Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, 36-1 Nishimachi, Yonago 683-8504, Japan
² Pharmaceutics, Division of Clinical Pharmacy, Dept of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan

^* To whom correspondence should be addressed. E-mail: burioka{at}grape.med.tottori-u.ac.jp.

	Abstract

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, we examined Period1 (Per1) mRNA expression in vitro and in vivo.

In 8 healthy subjects and 8 OSAS patients, we measured plasma noradrenaline, serum IL-6, and high-sensitivity CRP (hs-CRP), and Per1 mRNA expression in peripheral whole blood. 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, hs-CRP and plasma noradrenaline were elevated in OSAS patients, but improved by CPAP therapy. Per1 mRNA expression in the peripheral blood at 2:00 h significantly decreased by CPAP in OSAS patients. The stimulation with IL-6 did not directly induce Per1 mRNA in vitro. The administration of noradrenaline induced Per1 mRNA in cerebral cortex of mice in vivo.

We first revealed that OSAS caused clock gene dysfunction, and CPAP helped to improve it. Sympathetic activation and elevation of the plasma noradrenaline concentration in OSAS may be one of the factors involved in disorders of Per1 mRNA expression.

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