Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 37, Issue 1, Pages 62-75Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2011.11.018
Keywords
Antipsychotic; Clozapine; Dopamine D4 receptor gene (DRD4); Dopamine D5 receptor gene (DRD5); Pharmacogenetics; Response
Funding
- CIHR [200508GMH, MOP-15007]
- Novartis (Ciba-Geigy) Molecular Training Endowment
- NARSAD
- CAMH
- Eli Lilly
- American Foundation for Suicide Prevention
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Objectives: This study aimed to: 1) replicate previously reported associations between dopamine D4 receptor gene (DRD4) polymorphisms and antipsychotic (AP) response in a clozapine (CLZ) response sample; and 2) explore possible associations of polymorphisms across dopamine D5 receptor gene (DRD5) as well as other DRD4 regions. Methods: DRD4 exon III 48-bp, intron I (G)(n), and 120-bp repeat polymorphisms, and three DRD4 single nucleotide polymorphisms (SNPs); and DRD5 (CA/CT/GT)(n) microsatellite and four DRD5 SNPs were assessed using standard genotyping and statistical procedures. Results: We report evidence, which does not survive correction for multiple testing, supporting previous DRD4 findings. Findings of interest include the 120-bp 1-copy allele, intron I (G)(n) 142-bp/140-bp genotype, and exon III 4R allele with CLZ response. All DRD5 tests were negative. Conclusions: Overall, these results suggest a possible minor contribution of DRD4 variants, but not DRD5 variants, towards the AP/CLZ response phenotype. (c) 2011 Elsevier Inc. All rights reserved.
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