TY - JOUR
T1 - Association of the RGS2 gene with extrapyramidal symptoms induced by treatment with antipsychotic medication
AU - Greenbaum, Lior
AU - Strous, Rael D.
AU - Kanyas, Kyra
AU - Merbl, Yifat
AU - Horowitz, Anat
AU - Karni, Osnat
AU - Katz, Elena
AU - Kotler, Moshe
AU - Olender, Tsviya
AU - Deshpande, Smita N.
AU - Lancet, Doron
AU - Ben-Asher, Edna
AU - Lerer, Bernard
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - Akathisia
KW - Extrapyramidal symptoms
KW - Parkinsonism
KW - RGS2
KW - Regulators of G protein signaling
KW - Risperidone
KW - Typical antipsychotics
UR - http://www.scopus.com/inward/record.url?scp=34250213254&partnerID=8YFLogxK
U2 - 10.1097/FPC.0b013e32800ffbb4
DO - 10.1097/FPC.0b013e32800ffbb4
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AN - SCOPUS:34250213254
SN - 1744-6872
VL - 17
SP - 519
EP - 528
JO - Pharmacogenetics and Genomics
JF - Pharmacogenetics and Genomics
IS - 7
ER -