Association of prepro-orexin polymorphism with obstructive sleep
Weihu Chen, MD
, Jingying Ye, MD
, Demin Han, MD, PhD
, Guoping Yin, MD,
Boxuan Wang, MS, Yuhuan Zhang
Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otorhinolaryngology
Head and Neck Surgery, Ministry of Education, Beijing, China
Received 23 October 2010
Abstract Background: Because of the potential role of orexin neuronal circuitry in the regulation of sleep and
wakefulness and arousal and breathing, it seems reasonable to speculate that abnormalities in the
prepro-orexin gene could be relevant to studies of obstructive sleep apnea/hypopnea syndrome
(OSAHS); and it might be a candidate gene in the pathogenesis of OSAHS.
Objective: The present study investigated whether single nucleotide polymorphisms (SNPs) in the
human prepro-orexin gene are associated with OSAHS in Han Chinese people.
Methods: A total of 394 subjects (217 cases and 177 control subjects) were recruited from China.
Diagnostic polysomnography was performed in all patients and control subjects. SNPs in potentially
functional regions of the gene were identified; and genotypes, determined by direct sequencing.
Results: By sequencing the promoter, 2 exons, and the exon-intron junctions of the prepro-orexin
gene, the g11182CNT SNP was identified. Statistical analysis showed that there were significant
differences in the genotype distribution between patients with OSAHS and the control group
= 6.437, P = .04). Variant allele T of the g1182CNT polymorphism was more commonly
found in patients with OSAHS as compared with control subjects (χ
= 5.648, P = .017; odds
ratio, 1.449; 95% confidence interval, 1.0466–1.968).
Conclusions: Our results suggest that the prepro-orexin gene polymorphism g1182CNT is associated
with susceptibility to OSAHS in Han Chinese. This study provides insights into the genetic
information for future studies regarding this gene in OSAHS.
© 2012 Elsevier Inc. All rights reserved.
Obstructive sleep apnea/hypopnea syndrome (OSAHS) is
a highly prevalent disorder with multiple comorbidities.
Overt sleep apnea has been estimated to affect 2% of middle-
aged women and 4% of middle-aged men, at least 1% of
preschool children, and at least 11% of the elderly [1-3]. Its
etiology is complex and multifactorial, with evidence that
susceptibility is influenced by risk factors that include
obesity and obesity-associated traits, craniofacial character-
istics associated with reduced upper airway dimensions, as
well as ventilatory deficits that predispose to pharyngeal
collapsibility during sleep, when neuromuscular output is
either reduced or relatively unstable. Although studies of the
genetic etiology of the disorder are few, there are growing
data that have quantified the heritability of OSAHS,
described potential modes of transmission, and have
identified suggestive and/or biologically plausible candidate
Available online at www.sciencedirect.com
American Journal of Otolaryngology–Head and Neck Medicine and Surgery 33 (2012) 31 – 36
The source of financial support: This work was supported by the
National Natural Science Foundation of China (Grant no. 30730100).
Corresponding author. Department of Otorhinolaryngology, Head and
Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key
Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of
Education, Beijing 100730, China. Tel.: +86 10 58265782; fax: +86 10
E-mail address: firstname.lastname@example.org (D. Han).
Co–first author: Chen Weihu, MD, and Ye Jingying, MD, contributed
equally to this work.
0196-0709/$ – see front matter © 2012 Elsevier Inc. All rights reserved.