This study was supported by a grant-in-aid for the 21st Century Center of Excellence Program of Fujita Health University from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The study was also supported in part by a grant from the Society for Promotion of International Oto-Rhino-Laryngology, Japan. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
A functional variation in the hypocretin neuropeptide precursor gene may be associated with obstructive sleep apnea syndrome in Japan†
Article first published online: 2 FEB 2012
Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
Volume 122, Issue 4, pages 925–929, April 2012
How to Cite
Ahmed, W. A., Tsutsumi, M., Nakata, S., Mori, T., Nishimura, Y., Fujisawa, T., Kato, I., Nakashima, M., Kurahashi, H. and Suzuki, K. (2012), A functional variation in the hypocretin neuropeptide precursor gene may be associated with obstructive sleep apnea syndrome in Japan. The Laryngoscope, 122: 925–929. doi: 10.1002/lary.23179
- Issue published online: 20 MAR 2012
- Article first published online: 2 FEB 2012
- Manuscript Accepted: 7 DEC 2011
- Manuscript Received: 9 NOV 2011
- Obstructive sleep apnea syndrome;
- hypocretin neuropeptide precursor gene;
- reporter gene assay;
- functional variation;
- Level of Evidence: 2b
To evaluate the association of hypocretin neuropeptide precursor gene (HCRT) variations with obstructive sleep apnea syndrome (OSAS) in a cohort of Japanese patients and to further evaluate whether the significant HCRT variations have potential functional consequences on HCRT expression.
Case-control genetic association study.
We studied the genetic variations within the HCRT gene. The study population consisted of 100 OSAS patients and 100 control subjects. The HCRT gene was amplified by polymerase chain reaction in all study subjects followed by direct sequencing and analysis of sequencing data.
Two genetic variations within the HCRT intron, IVS1+16T>C (rs9902709) and IVS1−69G>C, were identified with significant differences between patients and controls (P < .05). A reporter gene assay using HeLa cells showed that the construct containing the C allele of the rs9902709 variation had significantly higher luciferase activity compared with the construct containing the T allele (P = .002). Furthermore, enzyme immunoassay revealed that subjects with T/C and C/C genotypes for rs9902709 had 1.4-fold and 1.5-fold increases in sera levels of orexin-A, respectively.
Our genetic association study, followed by functional and quantitative phenotyping assays, demonstrated a functional locus within the HCRT gene, which may act to increase HCRT expression and lead to a protective effect against the development of OSAS. Laryngoscope, 2012