0743 ASSOCIATION ANALYSIS OF MAP2K5 VARIANTS WITH RESTLESS LEG SYNDROME IN THE KOREAN POPULATION

Abstract

Restless legs syndrome (RLS) is a neurological disorder characterized by unpleasant sensations in the legs and a strong urge to move them. Because its symptoms occur primarily when a person is relaxing, it usually interferes with sleep and is considered a sleep disorder. Previous studies of RLS have reported the presence of a positive family history suggesting a genetic involvement in the etiology of RLS. Moreover, recent genetic researches have reveled several genes, such as MEIS1, BTBD9 and MAP2K5, as potentially associated with RLS. The MAP2K5 gene has been also identified as a possible RLS susceptibility gene in genome-wide association analyses. The goal of the present study is to evaluate the association of MAP2K5 variants with RLS in the Korean population. Based on previous results, we selected four single nucleotide polymorphisms (SNPs), rs6494696, rs12593813, rs11635424 and rs1026732, in the MAP2K5 gene on chromosome 15. The study included 268 RLS patients and 229 healthy controls. We performed case-control association and case-control haplotype analyses of the four MAP2K5 variants. The genotype distributions of all four SNPs followed the Hardy-Weinberg equilibrium. Case-control association study analyses were performed with recessive, dominant, genotype, and allele models, and no significant genetic differences were found between patients with RLS and healthy controls with respect to all four SNPs. However, rs6494696, rs12593813, rs11635424 and rs1026732 showed significant association (overall P = 1.37E-39; permutation P = 0) in a case-control haplotype analysis with the expectation-maximization algorithm. The haplotype analysis results suggest that MAP2K5 variants rs6494696, rs12593813, rs11635424 and rs1026732 may confer susceptibility for RLS in the Korean population. Association analysis revealed a probable genetic difference between Korean and Caucasian populations in the degree of MAP2K5 involvement in RLS pathogenesis.