Restless legs syndrome-associated MEIS1 risk variant influences iron homeostasis

Ann Neurol. 2011 Jul;70(1):170-5. doi: 10.1002/ana.22435. Epub 2011 Jun 27.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Iron-Deficiency / genetics
  • Anemia, Iron-Deficiency / metabolism
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Cells, Cultured
  • Genetic Variation / genetics*
  • HeLa Cells
  • Homeodomain Proteins / genetics*
  • Homeostasis* / genetics
  • Humans
  • Iron / metabolism*
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins / genetics*
  • Restless Legs Syndrome / genetics*
  • Restless Legs Syndrome / metabolism*
  • Risk Factors
  • Transcription Factors

Substances

  • Caenorhabditis elegans Proteins
  • Homeodomain Proteins
  • MEIS1 protein, human
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins
  • Transcription Factors
  • Unc-62 protein, C elegans
  • Iron