The BTBD9 gene may be associated with antipsychotic-induced restless legs syndrome in schizophrenia.
OBJECTIVE
A genome-wide association study and several replication studies have shown significant association between BTBD9 gene single nucleotide polymorphisms and restless legs syndrome (RLS). The aim of this study is to investigate the association between the BTBD9 gene polymorphisms and antipsychotic-induced RLS in schizophrenic patients.


METHODS
Restless legs syndrome symptoms were evaluated using the diagnostic criteria of the International Restless Legs Syndrome Study Group in 190 Korean schizophrenic patients. We genotyped the rs9357271 and rs3923809 polymorphisms of the BTBD9 gene in schizophrenic patients with (n = 96) and without (n = 94) RLS symptoms.


RESULTS
There was a significant difference in the allele frequency (χ(2) = 8.14, p = 0.004) of the rs9357271 polymorphism between schizophrenic patients with and without RLS symptoms. Significant genotypic association of this single nucleotide polymorphisms with RLS symptoms was also observed for the dominant model (χ(2) = 10.32, p = 0.001) and heterozygous model (χ(2) = 10.9, p = 0.001). When we compared the frequencies of the rs3923809-rs9357271 haplotypes between the two groups, the overall haplotype frequencies were significantly different (permuted p = 0.037), and the A-T haplotype was significantly more frequent in the RLS symptom group than in the no RLS symptom group (0.112 vs. 0.041, permuted p = 0.007).


CONCLUSIONS
These data suggest that the BTBD9 gene is associated with antipsychotic-induced RLS symptoms in schizophrenic patients.
Department of Psychiatry, Gachon University, School of Medicine, Incheon, Korea.
Seung-Gul
SG
Kang
Heon-Jeong
HJ
Lee
Young-Min
YM
Park
Hee Jung
HJ
Yang
Hyun Mi
HM
Song
Yu Jin
YJ
Lee
Seong-Jin
SJ
Cho
Sung Nam
SN
Cho
Leen
L
Kim
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012148:Restless Legs Syndrome / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
D014150:Antipsychotic Agents; C522207:BTBD9 protein, human; D009419:Nerve Tissue Proteins; D014157:Transcription Factors