RT Journal Article SR Electronic T1 MEIS1 and BTBD9: genetic association with restless leg syndrome in end stage renal disease JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 462 OP 466 DO 10.1136/jmg.2010.087858 VO 48 IS 7 A1 Schormair, Barbara A1 Plag, Jens A1 Kaffe, Maria A1 Groß, Nadine A1 Czamara, Darina A1 Samtleben, Walter A1 Lichtner, Peter A1 Ströhle, Andreas A1 Stefanidis, Ioannis A1 Vainas, Andreas A1 Dardiotis, Efthimios A1 Sakkas, George K A1 Gieger, Christian A1 Müller-Myhsok, Bertram A1 Meitinger, Thomas A1 Heemann, Uwe A1 Hadjigeorgiou, Georgios M A1 Oexle, Konrad A1 Winkelmann, Juliane YR 2011 UL http://jmg.bmj.com/content/48/7/462.abstract AB 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 (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.