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Objective: Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population.

Methods: We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results.

Results: In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10) in on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10) and rs9390170 (OR=0.6778, p=7.67×10) in on chromosome 6q24. From the replication samples, we found rs9390170 in (p=0.036) and rs3923809 and rs9296249 in (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10) in was associated with RLS.

Conclusion: From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by , is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.