Association of the RGS2 gene with extrapyramidal symptoms induced by treatment with antipsychotic medication

Pharmacogenet Genomics. 2007 Jul;17(7):519-28. doi: 10.1097/FPC.0b013e32800ffbb4.


Objectives: To investigate the role of genes encoding regulators of G protein signaling in early therapeutic response to antipsychotic drugs and in susceptibility to drug-induced extrapyramidal symptoms. As regulators of G protein signaling and regulators of G protein signaling-like proteins play a pivotal role in dopamine receptor signaling, genetically based, functional variation could contribute to interindividual variability in therapeutic and adverse effects.

Methods: Consecutively hospitalized, psychotic patients with Diagnostic and Statistical Manual of Mental Disorder-IV schizophrenia (n=121) were included in the study if they received treatment with typical antipsychotic medication (n=72) or typical antipsychotic drugs and risperidone (n=49) for at least 2 weeks. Clinical state and adverse effects were rated at baseline and after 2 weeks. Twenty-four single nucleotide polymorphisms were genotyped in five regulators of G protein signaling genes.

Results: None of the single nucleotide polymorphisms were related to clinical response to antipsychotic treatment at 2 weeks. Five out of six single nucleotide polymorphisms within or flanking the RGS2 gene were nominally associated with development or worsening of parkinsonian symptoms (PARK+) as measured by the Simpson Angus Scale, one of them after correction for multiple testing (rs4606, P=0.002). A GCCTG haplotype encompassing tagging single nucleotide polymorphisms within and flanking RGS2 was significantly overrepresented among PARK+ compared with PARK--patients (0.23 vs. 0.08, P=0.003). A second, 'protective', GTGCA haplotype was significantly overrepresented in PARK--patients (0.13 vs. 0.30, P=0.009). Both haplotype associations survive correction for multiple testing.

Conclusions: Subject to replication, these findings suggest that genetic variation in the RGS2 gene is associated with susceptibility to extrapyramidal symptoms induced by antipsychotic drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / pharmacokinetics
  • Extrapyramidal Tracts / drug effects
  • Female
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide
  • RGS Proteins / genetics*
  • Risperidone / adverse effects
  • Risperidone / pharmacokinetics
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics
  • Schizophrenia / metabolism


  • Antipsychotic Agents
  • RGS Proteins
  • RGS2 protein, human
  • Risperidone