title: Susceptible genes of restless legs syndrome in migraine.
abstract: Objective Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). The aim of the present study was to determine if these genetic variants were also associated with the comorbidity of RLS and migraine in patients. Methods Thirteen single-nucleotide polymorphisms (SNPs) at six RLS risk loci ( MEIS1, BTBD9, MAP2K5, PTPRD, TOX3, and an intergenic region on chromosome 2p14) were genotyped in 211 migraine patients with RLS and 781 migraine patients without RLS. Association analyses were performed for the overall cohort, as well as for the subgroups of patients who experienced migraines with and without aura and episodic migraines (EMs) vs. chronic migraines (CMs). In order to verify which genetic markers were potentially related to the incidence of RLS in migraine patients, multivariate regression analyses were also performed. Results Among the six tested loci, only MEIS1 was significantly associated with RLS. The most significant SNP of MEIS1, rs2300478, increased the risk of RLS by 1.42-fold in the overall cohort ( p = 0.0047). In the subgroup analyses, MEIS1 augmented the risk of RLS only in the patients who experienced EMs (odds ratio (OR) = 1.99, p = 0.0004) and not those experiencing CMs. Multivariate regression analyses further showed that rs2300478 in MEIS1 (OR = 1.39, p = 0.018), a CM diagnosis (OR = 1.52, p = 0.022), and depression (OR = 1.86, p = 0.005) were independent predictors of RLS in migraine. Conclusions MEIS1 variants were associated with an increased risk of RLS in migraine patients. It is possible that an imbalance in iron homeostasis and the dopaminergic system may represent a link between RLS incidence and migraines.
authors.affiliation: 1 Department of Neurology, Neurological Institute, Taipei-Veterans General Hospital, Taiwan.|2 Faculty of Medicine, National Yang-Ming University School of Medicine, Taiwan.
authors.forename: Jong-Ling
authors.initials: JL
authors.lastname: Fuh
authors.affiliation: 3 Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taiwan.|4 Department of Medical Research and Education, Taipei-Veterans General Hospital, Taiwan.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Chung
authors.affiliation: 1 Department of Neurology, Neurological Institute, Taipei-Veterans General Hospital, Taiwan.|2 Faculty of Medicine, National Yang-Ming University School of Medicine, Taiwan.
authors.forename: Shu-Chih
authors.initials: SC
authors.lastname: Yao
authors.affiliation: 5 Department of Neurology, Lin-Shin Hospital, Taiwan.
authors.forename: Ping-Kun
authors.initials: PK
authors.lastname: Chen
authors.affiliation: 1 Department of Neurology, Neurological Institute, Taipei-Veterans General Hospital, Taiwan.|2 Faculty of Medicine, National Yang-Ming University School of Medicine, Taiwan.
authors.forename: Yi-Chu
authors.initials: YC
authors.lastname: Liao
authors.affiliation: 6 Institute of Biomedical Sciences, Academia Sinica, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: 7 Living Water Neurological Clinic, Taiwan.
authors.forename: Po-Jen
authors.initials: PJ
authors.lastname: Wang
authors.affiliation: 1 Department of Neurology, Neurological Institute, Taipei-Veterans General Hospital, Taiwan.|2 Faculty of Medicine, National Yang-Ming University School of Medicine, Taiwan.
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Wang
authors.affiliation: 1 Department of Neurology, Neurological Institute, Taipei-Veterans General Hospital, Taiwan.|2 Faculty of Medicine, National Yang-Ming University School of Medicine, Taiwan.
authors.forename: Shih-Pin
authors.initials: SP
authors.lastname: Chen
authors.affiliation: 6 Institute of Biomedical Sciences, Academia Sinica, Taiwan.
authors.forename: Cathy S-J
authors.initials: CS
authors.lastname: Fann
authors.affiliation: 3 Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taiwan.
authors.forename: Lung-Sen
authors.initials: LS
authors.lastname: Kao
authors.affiliation: 1 Department of Neurology, Neurological Institute, Taipei-Veterans General Hospital, Taiwan.|2 Faculty of Medicine, National Yang-Ming University School of Medicine, Taiwan.
authors.forename: Shuu-Jiun
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D017677:Age Distribution; D015984:Causality; D015897:Comorbidity; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D012148:Restless Legs Syndrome / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D017678:Sex Distribution; D013624:Taiwan / Q000453:epidemiology
chemical_list: D005819:Genetic Markers; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein
keywords: Migraine; depression; iron metabolism; restless legs syndrome; single-nucleotide polymorphism