A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms.
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.
Gassó
P
P
Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Barcelona, Spain.
Mas
S
S
Bernardo
M
M
Alvarez
S
S
Parellada
E
E
Lafuente
A
A
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001480:Basal Ganglia Diseases / Q000139:chemically induced*; D002874:Chromosome Mapping; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D018967:Risperidone / Q000009:adverse effects*
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; D050637:Receptors, Dopamine D3; D018967:Risperidone