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Sci Rep. 2017 Apr 20;7:46620. doi: 10.1038/srep46620.

MEIS1 variant as a determinant of autonomic imbalance in Restless Legs Syndrome.

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INSERM U1046, UMR CNRS 9214, University of Montpellier, 371, avenue du doyen Gaston Giraud, 34295 Montpellier Cedex 05, France.
Institut Montpelliérain Alexander Grothendieck, CNRS, University of Montpellier, Department of Statistics, Montpellier, France.
INSERM U1051, Institute for Neurosciences of Montpellier (INM), 80 rue Augustin Fliche, 34091 Montpellier, France.
Institute for Neurogenomic, Helmholtz Zentrum München, Neuherberg; Neurologische Klinik und Poliklinik Munich, Germany.
Sleep Unit, Department of Neurology, Gui-de-Chauliac hospital, INSERM U1061, Montpellier, France.


Restless Legs Syndrome (RLS) is a genetically complex neurological disorder in which overlapping genetic risk factors may contribute to the diversity and heterogeneity of the symptoms. The main goal of the study was to investigate, through analysis of heart rate variability (HRV), whether in RLS patients the MEIS1 polymorphism at risk influences the sympathovagal regulation in different sleep stages. Sixty-four RLS patients with periodic leg movement index above 15 per hour, and 38 controls underwent one night of video-polysomnographic recording. HRV in the frequency- and time- domains was analyzed during nighttime sleep. All RLS patients were genotyped, and homozygotes for rs2300478 in the MEIS1 locus were used for further analysis. Comparison of the sympathovagal pattern of RLS patients to control subjects did not show significant differences after adjustments for confounding factors in frequency-domain analyses, but showed an increased variability during N2 and N3 stages in time-domain analyses in RLS patients. Sorting of RLS patients according to MEIS1 polymorphism reconfirmed the association between MEIS1 and PLMS, and showed a significant increased sympathovagal balance during N3 stage in those homozygotes for the risk allele. RLS patients should be considered differently depending on MEIS1 genotype, some being potentially at risk for cardiovascular disorders.

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