title: Restless legs syndrome-associated MEIS1 risk variant influences iron homeostasis.
abstract: Restless legs syndrome (RLS) is a frequent sleep disorder that is linked to disturbed iron homeostasis. Genetic studies identified MEIS1 as an RLS-predisposing gene, where the RLS risk haplotype is associated with decreased MEIS1 mRNA and protein expression. We show here that RNA interference treatment of the MEIS1 worm orthologue increases ferritin expression in Caenorhabditis elegans and that the RLS-associated haplotype leads to increased expression of ferritin and DMT1 in RLS brain tissues. Additionally, human cells cultured under iron-deficient conditions show reduced MEIS1 expression. Our data establish a link between the RLS MEIS1 gene and iron metabolism.
authors.affiliation: Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Catoire
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dion
authors.forename: Lan
authors.initials: L
authors.lastname: Xiong
authors.forename: Mourabit
authors.initials: M
authors.lastname: Amari
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gaudet
authors.forename: Simon L
authors.initials: SL
authors.lastname: Girard
authors.forename: Anne
authors.initials: A
authors.lastname: Noreau
authors.forename: Claudia
authors.initials: C
authors.lastname: Gaspar
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.forename: Jacques Y
authors.initials: JY
authors.lastname: Montplaisir
authors.forename: J Alex
authors.initials: JA
authors.lastname: Parker
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002478:Cells, Cultured; D014644:Genetic Variation / Q000235:genetics*; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D012148:Restless Legs Syndrome / Q000235:genetics* / Q000378:metabolism*; D012307:Risk Factors; D014157:Transcription Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors; C109537:Unc-62 protein, C elegans; D007501:Iron