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

Lior Greenbaum, Rael D. Strous, Kyra Kanyas, Yifat Merbl, Anat Horowitz, Osnat Karni, Elena Katz, Moshe Kotler, Tsviya Olender, Smita N. Deshpande, Doron Lancet, Edna Ben-Asher, Bernard Lerer

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)519-528
Number of pages10
JournalPharmacogenetics and Genomics
Volume17
Issue number7
DOIs
StatePublished - Jul 2007

Keywords

  • Akathisia
  • Extrapyramidal symptoms
  • Parkinsonism
  • RGS2
  • Regulators of G protein signaling
  • Risperidone
  • Typical antipsychotics

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