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.