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

• DOI: 10.1038/tpj.2009.26
• Publication Date: 2009-06-09T09:58:27Z
• Authors: P Gassó; S Mas; M Bernardo; S Álvarez; E Parellada; A Lafuente
• Keywords: Adult; Receptors, Dopamine D3; Chromosome Mapping; Risperidone; Polymorphism, Single Nucleotide; Linkage Disequilibrium; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Basal Ganglia Diseases; Humans; Antipsychotic Agents

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 < or = 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 x 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.