Searching for functional SNPs or rare variants in exonic regions of DRD3 in risperidone-treated patients

Gassó, Patricia; Mas, Sergi; Oliveira, Cristina; Bioque, Miquel; Parellada, Eduard; Bernardo, Miquel; Trias, Gemma; Comeche, Joaquim; Lafuente, Amalia

doi:10.1016/j.euroneuro.2010.06.006

« Previous Next »European Neuropsychopharmacology
Volume 21, Issue 4 , Pages 294-299, April 2011

Searching for functional SNPs or rare variants in exonic regions of DRD3 in risperidone-treated patients

Patricia Gassó
- Dept. of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Casanova 143, E-08036 Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBER-SAM), Spain
Sergi Mas
- Dept. of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Casanova 143, E-08036 Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBER-SAM), Spain
Cristina Oliveira
- Psychiatry Service, Hospital Clinic de Barcelona, Villarroel 170, E-08036 Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBER-SAM), Spain
Miquel Bioque
- Psychiatry Service, Hospital Clinic de Barcelona, Villarroel 170, E-08036 Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBER-SAM), Spain
Eduard Parellada
- Psychiatry Service, Hospital Clinic de Barcelona, Villarroel 170, E-08036 Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBER-SAM), Spain
Miquel Bernardo
- Psychiatry Service, Hospital Clinic de Barcelona, Villarroel 170, E-08036 Barcelona, Spain
- Dept. of Psychiatry and Clinical Psychobiology, University of Barcelona, Casanova 143, E-08036 Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBER-SAM), Spain
Gemma Trias
- Dept. of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Casanova 143, E-08036 Barcelona, Spain
Joaquim Comeche
- Dept. of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Casanova 143, E-08036 Barcelona, Spain
Amalia Lafuente
- Dept. of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Casanova 143, E-08036 Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBER-SAM), Spain
- Corresponding author. Dept. of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, IDIBAPS, Casanova 143, E-08036 Barcelona, CIBER-SAM (Centro de Investigación Biomédica en Red de Salud Mental, Spanish Ministry of Health, Instituto Carlos III), Spain. Tel.: +34 0034934024526; fax: +34 0034934035881.

Received 16 February 2010; received in revised form 30 April 2010; accepted 12 June 2010. published online 09 July 2010.

Abstract

Previously one intronic DRD3 SNP, rs167771, was associated with risperidone-induced extrapyramidal side-effects (EPS). The aim of the present study was to search hitherto unidentified common functional variants or rare variants, in DRD3 associated with risperidone-induced EPS. 126 subjects treated with risperidone participated in this study. We sequenced the seven exons of DRD3. After sequencing we localized five dbSNPs and four new rare variants. None of the dSNPs or rare variants seems to be functional after bioinformatics analysis. Our results suggest that, rather than exonic regions, regulatory regions and introns could be related to the associations reported for DRD3 and the incidence of locomotor side-effects.

Keywords: Risperidone, Extrapyramidal side-effects, Schizophrenia, DRD3, Single nucleotide polymorphism, Rare variant, Resequencing, Pharmacogenetics