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A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms

Abstract

We present a pharmacogenetic study of acute antipsychotic (AP)-induced extrapyramidal symptoms (EPS) using an extensive linkage disequilibrium mapping approach in seven-candidate genes with a well-established link to dopamine (DRD2, DRD3, ACE, COMT, DAT, MAO-A, MAO-B). From a cohort of 321 psychiatric inpatients, 81 cases presenting with EPS (Simpson–Angus >3) and 189 controls presenting without EPS (Simpson–Angus 3) took part. Eighty-four-tag single nucleotide polymorphisms (SNPs) in candidate genes were genotyped. After extensive data cleaning, 70 SNPs were analyzed for association of single markers and haplotypes. AP dosage, AP-DRD2 blockade potency and age were identified as susceptibility factors for AP-induced EPS. One SNP of the DRD3 gene, rs167771, achieved significant association with EPS risk after Bonferroni correction (nominal P-value 1.3 × 10−4) in the patients treated with risperidone (132 patients). AP-induced EPS remains a serious public health problem. Our finding of a common SNP (rs167771) in the DRD3 gene provides a strong new candidate gene for risperidone-induced EPS.

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Acknowledgements

The authors thank the Language Advisory Service at the University of Barcelona, Spain for manuscript revision. This study was supported by the Spanish Ministry of Health, Instituto Carlos III (FIS, Fondo de Investigacion Sanitaria P1060182U-2006) and the Catalan Ministry of Innovation, Universities and Enterprise (DURSI, GRC2005SGR00039, GRC2005SGR00223).

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Gassó, P., Mas, S., Bernardo, M. et al. A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms. Pharmacogenomics J 9, 404–410 (2009). https://doi.org/10.1038/tpj.2009.26

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