Association of BTBD9 and MAP2K5/SKOR1 With Restless Legs Syndrome in Chinese Population

Sleep. 2017 Apr 1;40(4). doi: 10.1093/sleep/zsx028.


Study objectives: The aim of the study was to investigate the relationship between genetic factors and primary restless legs syndrome (RLS) in Chinese population.

Methods: A total of 116 RLS patients and 200 controls were recruited and the diagnosis of RLS was based on the criteria of International RLS Study Group. Polymer chain reaction (PCR) and sequencing were used to detect 19 single nucleotide polymorphisms (SNPs) in six genetic loci (MEIS1, BTBD9, PTPRD, MAP2K5/SKOR1, TOX3, and Intergenic region of 2p14).

Results: Our study found that one SNP increased the risk of RLS in Chinese population: rs6494696 of MAP2K5/SKOR1 (odds ratio [OR] = 0.09, p < .0001, recessive model). A further meta-analysis of RLS in Asian population found that two SNPs of BTBD9 increased the risk of RLS: rs9296249 of BTBD9 (OR = 1.44, p = .000, T allele), rs9357271 of BTBD9 (OR = 1.38, p = .021, dominant model).

Conclusion: Our results confirmed the association of BTBD9 and MAP2K5/SKOR1 with primary RLS in Chinese population.

Keywords: BTBD9; Genetic risk factors; MAP2K5/SKOR1.; Restless legs syndrome; SNPs.

MeSH terms

  • Alleles
  • Apoptosis Regulatory Proteins
  • Asian People / genetics*
  • China / ethnology
  • Female
  • High Mobility Group Proteins
  • Humans
  • MAP Kinase Kinase 5 / genetics*
  • Male
  • Middle Aged
  • Myeloid Ecotropic Viral Integration Site 1 Protein / genetics
  • Nerve Tissue Proteins
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics
  • Receptors, Progesterone / genetics
  • Restless Legs Syndrome / genetics*
  • Trans-Activators
  • Transcription Factors / genetics*


  • Apoptosis Regulatory Proteins
  • BTBD9 protein, human
  • High Mobility Group Proteins
  • MEIS1 protein, human
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Nerve Tissue Proteins
  • Receptors, Progesterone
  • TOX3 protein, human
  • Trans-Activators
  • Transcription Factors
  • MAP Kinase Kinase 5
  • MAP2K5 protein, human
  • PTPRD protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2