Association study between antipsychotics- induced restless legs syndrome and polymorphisms of dopamine D1, D2, D3, and D4 receptor genes in schizophrenia

Neuropsychobiology. 2008;57(1-2):49-54. doi: 10.1159/000129667. Epub 2008 May 2.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Antipsychotic Agents / adverse effects*
  • Brief Psychiatric Rating Scale
  • Diagnosis, Differential
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Receptors, Dopamine / genetics*
  • Receptors, Dopamine D1 / genetics*
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D3 / genetics*
  • Receptors, Dopamine D4 / genetics*
  • Restless Legs Syndrome / chemically induced*
  • Restless Legs Syndrome / diagnosis
  • Schizophrenia* / diagnosis
  • Schizophrenia* / drug therapy
  • Schizophrenia* / genetics

Substances

  • Antipsychotic Agents
  • DRD3 protein, human
  • DRD4 protein, human
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Dopamine D4