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.
- Restless legs syndrome
- end-stage renal disease
- genetic association studies
- movement disorders (other than Parkinson's)
- renal medicine
- genetic epidemiology
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BS and JP contributed equally.
Funding This study was supported in part (for GMH and ED) from University of Thessaly, Research Committee (Code 2845).
Competing interests WS has received lecture fees from Ortho Biotech, GE Health Care, Sanofi Aventis and Roche Pharma. TM, BMM, JW filed a patent regarding the publication Winkelmann et al 2007.
Ethics approval This study was conducted with the approval of the local ethics committees in Germany (Klinikum rechts der Isar, TU München) and in Greece (University of Thessaloniki).
Provenance and peer review Not commissioned; externally peer reviewed.