Association of candidate genetic variants with restless legs syndrome in end stage renal disease: a multicenter case-control study in Taiwan

Eur J Neurol. 2014 Mar;21(3):492-8. doi: 10.1111/ene.12337. Epub 2014 Jan 16.

Abstract

Background and purpose: Recent genome-wide association studies have shown associations between multiple genetic variants and primary restless legs syndrome (RLS). Their roles in end stage renal disease (ESRD) related secondary RLS are not clear and studies in Asian populations are scarce. The association between candidate genetic variants and uremic RLS was investigated in a large cohort of Taiwanese dialysis patients.

Methods: Sixteen RLS-related genetic variants at six loci, including MEIS1, BTBD9, MAP2K5/SKOR1, PTPRD, TOX3/BC034767 and the intergenic region of chromosome 2p14, in a total of 993 ESRD patients (259 subjects with and 734 subjects without RLS) were genotyped using TaqMan genotyping assays. Multivariate logistic regression analysis was used to test for associations between the genotypes and RLS in ESRD. Power calculations were completed using the CATs Genetic Power Calculator with settings of a multiplicative genetic model.

Results: A modest association between the PTPRD variant rs4626664 and uremic RLS (odds ratio 1.52, 95% CI 1.03-2.23, P = 0.03) and a trend that TOX3/BC034767 variant rs3104767 may associate with the occurrence of RLS were observed in our dialysis population (odds ratio 1.74, 95% CI 0.97-3.11, P = 0.06). No associations between other genetic variants and risk and severity of RLS were observed in our ESRD cohort.

Conclusions: The genetic variants of primary RLS candidate genes did not play a major role in our uremic RLS populations. The ethnic difference and heterogeneous etiologies underlying renal failure may partly explain the minor genetic contribution to uremic RLS in our populations. Further studies for other ethnicities will be of worth.

Keywords: BTBD9; MAP2K5; MEIS1; PTPRD; end stage renal disease; restless legs syndrome.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis Regulatory Proteins
  • Chromosomes, Human, Pair 2 / genetics
  • Female
  • Genetic Association Studies
  • Genetic Variation / genetics*
  • Genotype
  • High Mobility Group Proteins
  • Humans
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / genetics
  • Linkage Disequilibrium
  • Logistic Models
  • Male
  • Middle Aged
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics*
  • Receptors, Progesterone / genetics*
  • Restless Legs Syndrome / etiology*
  • Restless Legs Syndrome / genetics*
  • Retrospective Studies
  • Taiwan / epidemiology
  • Trans-Activators

Substances

  • Apoptosis Regulatory Proteins
  • High Mobility Group Proteins
  • Receptors, Progesterone
  • TOX3 protein, human
  • Trans-Activators
  • PTPRD protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2