title: Increased plasma orexin-A levels in patients with insomnia disorder are not associated with prepro-orexin or orexin receptor gene polymorphisms.
abstract: Orexins, also known as hypocretins, play a regulatory role in the sleep-wake cycle by activating orexin receptors. Previous animal studies have shown that sleep deprivation can elevate orexinergic peptide levels. However, the relationship between insomnia disorder and orexin-A levels in humans has not been explored. In the current study, we examined plasma orexin-A levels in patients with insomnia disorder and in normal sleepers. We also studied the possible mechanisms underlying changes in orexin-A levels between the study groups; this included investigations of prepro-orexin and orexin receptor gene polymorphisms as well as exploration of other variables. We measured plasma orexin-A levels in 228 patients with insomnia disorder and 282 normal sleepers. The results indicated that the patients with insomnia disorder had significantly higher orexin-A levels than normal sleepers (63.42±37.56 vs. 54.84±23.95pg/ml). A positive relationship was detected between orexin-A level and age in patients with insomnia disorder. Orexin-A levels were elevated in relation to course of insomnia, as well as in relation to increased Insomnia Severity Index score. None of the evaluated prepro-orexin gene single nucleotide polymorphisms were informative between the two study populations. After sequencing all orexin receptor exons, one variation (rs2271933) in the OX1R gene and one variation (rs2653349) in the OX2R gene were found. However, no significant differences were found in either genotypic or allelic frequency distributions between the two study groups. It is suggested that the increased plasma orexin-A levels in patients with insomnia disorder are associated with the course and severity of insomnia, but not with prepro-orexin and orexin receptor gene polymorphisms.
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Wei Qi Road, Jinan, Shandong 250021, PR China.
authors.forename: Shi
authors.initials: S
authors.lastname: Tang
authors.affiliation: Sleep Medicine Center, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Sleep Medicine Center, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Sleep Medicine Center, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Lu
authors.affiliation: Third People's Hospital of Jinan, 1 Wangsheren Northern Street, Jinan, Shandong 250100, PR China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Li
authors.affiliation: Shandong Mental Health Center, Shandong University, 49 Wenhua East Road, Jinan, Shandong 250014, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors.forename: Zhangning
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Duan
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Wei Qi Road, Jinan, Shandong 250021, PR China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Du
authors.affiliation: Sleep Medicine Center, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China; Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China. Electronic address: tjiyou@yahoo.com.
authors.forename: Jiyou
authors.initials: J
authors.lastname: Tang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D064446:Orexin Receptors / Q000097:blood / Q000235:genetics*; D000068797:Orexins / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D012890:Sleep / Q000235:genetics / Q000502:physiology; D012892:Sleep Deprivation / Q000235:genetics / Q000503:physiopathology; D007319:Sleep Initiation and Maintenance Disorders / Q000097:blood / Q000235:genetics* / Q000503:physiopathology
chemical_list: C578630:HCRTR1 protein, human; C578626:HCRTR2 protein, human; D064446:Orexin Receptors; D000068797:Orexins
keywords: Gene variations; Insomnia; Orexin receptors; Orexin-A; Prepro-orexin