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Restless legs syndrome-associated MEIS1 risk variant influences iron homeostasis

Authors

  • Hélène Catoire PhD,

    1. Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal
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  • Patrick A. Dion PhD,

    1. Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal
    2. Department of Pathology and Cell Biology, Faculty of Medicine, University of Montreal;
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  • Lan Xiong MD, PhD,

    1. Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal
    2. Department of Medicine, Faculty of Medicine, University of Montreal
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  • Mourabit Amari MD,

    1. Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal
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  • Rebecca Gaudet MSc,

    1. Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal
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  • Simon L. Girard MSc,

    1. Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal
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  • Anne Noreau MSc,

    1. Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal
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  • Claudia Gaspar PhD,

    1. Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal
    2. Department of Pathology and Cell Biology, Faculty of Medicine, University of Montreal;
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  • Gustavo Turecki MD, PhD,

    1. McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University
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  • Jacques Y. Montplaisir MD, PhD,

    1. Centre d'étude du sommeil, Hopital du Sacré-Coeur, Montreal
    2. Neurological Sciences Research Centre, University of Montreal; and
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  • J. Alex Parker PhD,

    1. Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal
    2. Department of Pathology and Cell Biology, Faculty of Medicine, University of Montreal;
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  • Guy A. Rouleau MD, PhD

    Corresponding author
    1. Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal
    2. Department of Medicine, Faculty of Medicine, University of Montreal
    3. Research Center, CHU Sainte-Justine, and Department of Pediatrics and Biochemistry, University of Montreal, Montreal, Quebec, Canada
    • Centre de Recherche du CHUM-Hopital Notre Dame, 1560 rue Sherbrooke Est, Montréal, Québec, Canada H2L 4M1
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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. Ann Neurol 2011;

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