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Objective Previous studies have suggested various causes of restless legs syndrome (RLS), including iron and dopamine concentrations in the brain. Genetic influences have also been reported in many studies. There is also a possibility that circadian clock genes may be involved because symptoms of RLS worsen at night. We investigated whether  CLOCK  and NPAS2 gene polymorphisms were associated with RLS.Methods A total of 227 patients with RLS and 229 non-RLS matched controls were assessed according to the International Restless Legs Syndrome Study Group diagnostic criteria. Genotyping was performed using reverse transcription polymerase chain reaction and high-resolution melting curve analyses.Results Although the genotype distributions of the  CLOCK  variants (rs1801260 and rs2412646) were not significantly different between patients with RLS and non-RLS controls, the allele frequencies of  CLOCK  rs1801260 showed marginally significant differences between the two groups (X 2  =2.98, p=0.085). Furthermore, there was a significant difference in the distribution of  CLOCK  haplotypes (rs1801260-rs2412646) between patients with RLS and non-RLS controls (p=0.013). The distributions of allelic, genotypic, and haplotypic variants of NPAS2 (rs2305160 and rs6725296) were not significantly different between the two groups.Conclusion Our results suggest that  CLOCK  variants may be associated with decreased susceptibility to RLS.

Association Between CLOCK Gene Variants and Restless Legs Syndrome in Koreans