MEIS1 and BTBD9 - genetic association with RLS in end-stage renal disease

Barbara Schormair (1) , Jens Plag (2) , Maria Kaffe (1) , Nadine Gross (3) , Darina Czamara (4) , Walter Samtleben (5) , Peter Lichtner (1) , Andreas Ströhle (2) , Ioannis Stefanidis (6) , Andreas Vainas (6) , Efthimios Dardiotis (7) , George K Sakkas (8) , Bertram Müller-Mhysok (4) , Thomas Meitinger (1) , Uwe Heemann (3) , Georgios M Hadjigeorgiou (9) , Konrad Oexle (10) , Juliane Winkelmann (11) , Christian Gieger (1)

1 Institute of Human Genetics
2 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
3 Department of Pulmonary Medicine
4 Max-Planck-Institut für Psychiatrie
5 Department of Internal Medicine, Nephrology Division, University of Munich - Klinikum Grosshadern
6 Department of Nephrology, Faculty of Medicine, University of Thessaly
7 Department of Neurology, Faculty of Medicine, University of Thessaly
8 Department of Nephrology, Faculty of Medicine, University of Thessaly
9 UTH - University of Thessaly [Volos]
10 Institute of Human Genetics, Technische Universität München
11 Institute of Bioinformatics and Systems Biology [München]

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, we performed a case-control association study of these variants in ESRD patients. Methods: We genotyped ten 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 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 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 (Pnom ≤ 0.004, ORs = 1.52 and 1.55), whereas, in the Greek sample, there was a trend for association to MAP2K5/SKOR1 and BTBD9 (Pnom ≤ 0.08, ORs = 1.41 and 1.33). In the combined analysis including all samples, BTBD9 was associated after correction for multiple testing (Pcorrected = 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.

Mots clés: Movement disorders (other than Parkinsons); Renal Medicine; Genetic epidemiology

Barbara Schormair, Jens Plag, Maria Kaffe, Nadine Gross, Darina Czamara, et al.. MEIS1 and BTBD9 - genetic association with RLS in end-stage renal disease. Journal of Medical Genetics, 2011, 48 (7), pp.462. ⟨10.1136/jmg.2010.087858⟩. ⟨hal-00632283⟩