Association study between antipsychotics- induced restless legs syndrome and polymorphisms of dopamine D1, D2, D3, and D4 receptor genes in schizophrenia.
OBJECTIVE
The cause of restless legs syndrome (RLS) is not yet clear, but more promising theories involve dopaminergic deficiency and genetic causes. This study investigated whether single-nucleotide polymorphisms in the genes of dopamine receptors DRD1, DRD2, DRD3 and DRD4 are associated with antipsychotics-induced RLS in schizophrenia.


METHODS
We evaluated 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group and its rating scale for RLS. Genotyping was performed for the DRD1 gene -48A/G, DRD2 gene TaqI A, DRD3 gene Ser9Gly and DRD4 gene -521C/T single-nucleotide polymorphisms. The method of multifactor dimensionality reduction was used to analyze gene-gene interactions.


RESULTS
We classified the schizophrenic patients into 96 with and 94 without RLS symptoms. The genotype frequencies of all polymorphisms investigated did not differ significantly between these 2 groups. MDR analysis did not show a significant effect of the 4 dopamine receptor gene variants on susceptibility to antipsychotic-induced RLS symptoms (p > 0.05).


CONCLUSIONS
These genetics data suggest that the analyzed polymorphisms of the dopamine genes may not be associated with RLS symptoms in schizophrenia. Confirming the results reported here requires a larger-scale study involving patients taking specific antipsychotics.
Kang
Seung-Gul
SG
Department of Psychiatry, Korea University College of Medicine, Seoul, South Korea.
Lee
Heon-Jeong
HJ
Choi
Jung-Eun
JE
Park
Young-Min
YM
Park
Jeong-Hyun
JH
Han
Changsu
C
Kim
Yong-Ku
YK
Kim
Seung-Hyun
SH
Lee
Min-Soo
MS
Joe
Sook-Haeng
SH
Jung
In-Kwa
IK
Kim
Leen
L
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D010054:Brief Psychiatric Rating Scale; D003937:Diagnosis, Differential; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011954:Receptors, Dopamine / Q000235:genetics*; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012148:Restless Legs Syndrome / Q000139:chemically induced* / Q000175:diagnosis; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; C493599:DRD4 protein, human; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4