title: miRNA profiles in plasma from patients with sleep disorders reveal dysregulation of miRNAs in narcolepsy and other central hypersomnias.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) have been implicated in the pathogenesis of human diseases including neurological disorders. The aim is to address the involvement of miRNAs in the pathophysiology of central hypersomnias including autoimmune narcolepsy with cataplexy and hypocretin deficiency (type 1 narcolepsy), narcolepsy without cataplexy (type 2 narcolepsy), and idiopathic hypersomnia.
  
  
  METHODS
  We conducted high-throughput analysis of miRNA in plasma from three groups of patients-with type 1 narcolepsy, type 2 narcolepsy, and idiopathic hypersomnia, respectively-in comparison with healthy controls using quantitative real-time polymerase chain reaction (qPCR) panels.
  
  
  METHODS
  University hospital based sleep clinic and research laboratories.
  
  
  METHODS
  Twelve patients with type 1 narcolepsy, 12 patients with type 2 narcolepsy, 12 patients with idiopathic hypersomnia, and 12 healthy controls.
  
  
  RESULTS
  By analyzing miRNA in plasma with qPCR we identified 50, 24, and 6 miRNAs that were different in patients with type 1 narcolepsy, type 2 narcolepsy, and idiopathic hypersomnia, respectively, compared with healthy controls. Twenty miRNA candidates who fulfilled the criteria of at least two-fold difference and p-value < 0.05 were selected to validate the miRNA changes in an independent cohort of patients. Four miRNAs differed significantly between type 1 narcolepsy patients and healthy controls. Levels of miR-30c, let-7f, and miR-26a were higher, whereas the level of miR-130a was lower in type 1 narcolepsy than healthy controls. The miRNA differences were not specific for type 1 narcolepsy, since the levels of the four miRNAs were also altered in patients with type 2 narcolepsy and idiopathic hypersomnia compared with healthy controls.
  
  
  CONCLUSIONS
  The levels of four miRNAs differed in plasma from patients with type 1 narcolepsy, type 2 narcolepsy and idiopathic hypersomnia suggesting that alterations of miRNAs may be involved in the pathophysiology of central hypersomnias.
authors.forename: Anja
authors.initials: A
authors.lastname: Holm
authors.forename: Claus Heiner
authors.initials: CH
authors.lastname: Bang-Berthelsen
authors.forename: Stine
authors.initials: S
authors.lastname: Knudsen
authors.forename: Birgitte R
authors.initials: BR
authors.lastname: Kornum
authors.forename: Signe
authors.initials: S
authors.lastname: Modvig
authors.forename: Poul
authors.initials: P
authors.lastname: Jennum
authors.forename: Steen
authors.initials: S
authors.lastname: Gammeltoft
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002385:Cataplexy / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D020177:Idiopathic Hypersomnia / Q000097:blood / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D009290:Narcolepsy / Q000097:blood / Q000235:genetics*; D009479:Neuropeptides / Q000172:deficiency; D000068797:Orexins; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D009479:Neuropeptides; D000068797:Orexins
keywords: cataplexy; hypersomnia; hypocretin; miRNA; narcolepsy