Association between restless legs syndrome and CLOCK and NPAS2 gene polymorphisms in schizophrenia.
Previous studies have suggested that there is a genetic basis to restless legs syndrome (RLS) development. Occurrence of antipsychotic-induced RLS could also be due to differences in genetic susceptibility. We investigated whether CLOCK and NPAS2 gene polymorphisms are associated with RLS in schizophrenic patients on antipsychotics because RLS symptoms usually manifest during the evening and night. We assessed symptoms of RLS in 190 Korean schizophrenic patients on antipsychotics and divided the subjects into two groups according to the International Restless Legs Syndrome Study Group diagnostic criteria: (i) subjects who met all the criteria and (ii) the remaining subjects who did not meet all the criteria. We found a significant difference in the number of subjects with different genotype and allele carrier frequencies for the CLOCK gene (rs2412646) between the two groups (p = 0.031 and 0.010, respectively). Distribution of CLOCK haplotypes (rs2412646-rs1801260) was significantly different between schizophrenic patients with and without RLS (p = 0.021). However, the distributions of allelic, genotypic, and haplotypic variants of NPAS2 (rs2305160 and rs6725296) were not significantly different between the two groups. Our results suggest that CLOCK polymorphisms are associated with increased susceptibility of schizophrenic patients to RLS. We hypothesize that RLS in schizophrenia patients treated with antipsychotics may be a very mild akathisia that manifests during the night and is under control of circadian oscillation.
Department of Psychiatry, College of Medicine, Korea University , Seoul , South Korea .
Jin-Sook
JS
Jung
Heon-Jeong
HJ
Lee
Chul-Hyun
CH
Cho
Seung-Gul
SG
Kang
Ho-Kyoung
HK
Yoon
Young-Min
YM
Park
Joung-Ho
JH
Moon
Hee-Jung
HJ
Yang
Hyun-Mi
HM
Song
Leen
L
Kim
D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D056926:CLOCK Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012148:Restless Legs Syndrome / Q000150:complications / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D009419:Nerve Tissue Proteins; C104264:NPAS2 protein, human; C538943:CLOCK protein, human
Antipsychotics; CLOCK gene; circadian rhythm; restless legs syndrome