title: MEIS1 and BTBD9: genetic association with restless leg syndrome in end stage renal disease.
abstract: BACKGROUND
  Restless legs syndrome (RLS) is a sleep related movement disorder that occurs both in an idiopathic form and in symptomatic varieties. RLS is a frequent and distressing comorbidity in end stage renal disease (ESRD). For idiopathic RLS (iRLS), genetic risk factors have been identified, but their role in RLS in ESRD has not been investigated yet. Therefore, a case-control association study of these variants in ESRD patients was performed.
  
  
  METHODS
  The study genotyped 10 iRLS associated variants at four loci encompassing the genes MEIS1, BTBD9, MAP2K5/SKOR1, and PTPRD, in two independent case-control samples from Germany and Greece using multiplex PCR and MALDI-TOF (matrix assisted laser desorption/ionisation time-of-flight) mass spectrometry. Statistical analysis was performed as logistic regression with age and gender as covariates. For the combined analysis a Cochran-Mantel-Haenszel test was applied.
  
  
  RESULTS
  The study included 200 RLS-positive and 443 RLS-negative ESRD patients in the German sample, and 141 and 393 patients, respectively, in the Greek sample. In the German sample, variants in MEIS1 and BTBD9 were associated with RLS in ESRD (P(nom)≤0.004, ORs 1.52 and 1.55), whereas, in the Greek sample, there was a trend for association to MAP2K5/SKOR1 and BTBD9 (P(nom)≤0.08, ORs 1.41 and 1.33). In the combined analysis including all samples, BTBD9 was associated after correction for multiple testing (P(corrected)=0.0013, OR 1.47).
  
  
  CONCLUSIONS
  This is the first demonstration of a genetic influence on RLS in ESRD patients with BTBD9 being significantly associated. The extent of the genetic predisposition could vary between different subgroups of RLS in ESRD.
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München e German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Schormair
authors.forename: Jens
authors.initials: J
authors.lastname: Plag
authors.forename: Maria
authors.initials: M
authors.lastname: Kaffe
authors.forename: Nadine
authors.initials: N
authors.lastname: Gross
authors.forename: Darina
authors.initials: D
authors.lastname: Czamara
authors.forename: Walter
authors.initials: W
authors.lastname: Samtleben
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.forename: Andreas
authors.initials: A
authors.lastname: Ströhle
authors.forename: Ioannis
authors.initials: I
authors.lastname: Stefanidis
authors.forename: Andreas
authors.initials: A
authors.lastname: Vainas
authors.forename: Efthimios
authors.initials: E
authors.lastname: Dardiotis
authors.forename: George K
authors.initials: GK
authors.lastname: Sakkas
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Uwe
authors.initials: U
authors.lastname: Heemann
authors.forename: Georgios M
authors.initials: GM
authors.lastname: Hadjigeorgiou
authors.forename: Konrad
authors.initials: K
authors.lastname: Oexle
authors.forename: Juliane
authors.initials: J
authors.lastname: Winkelmann
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005858:Germany; D006115:Greece; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012148:Restless Legs Syndrome / Q000209:etiology* / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C522207:BTBD9 protein, human; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors