Dopamine D4 and D5 receptor gene variant effects on clozapine response in schizophrenia: Replication and exploration

Rudi Hwang*, Arun K. Tiwari, Clement C. Zai, Daniel Felsky, Eli Remington, Tessa Wallace, Ryan P. Tong, Renan P. Souza, Gabriel Oh, Steven G. Potkin, Jeffrey A. Lieberman, Herbert Y. Meltzer, James L. Kennedy

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)62-75
Number of pages14
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume37
Issue number1
DOIs
StatePublished - Apr 27 2012

Keywords

  • Antipsychotic
  • Clozapine
  • Dopamine D4 receptor gene (DRD4)
  • Dopamine D5 receptor gene (DRD5)
  • Pharmacogenetics
  • Response

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

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    Hwang, R., Tiwari, A. K., Zai, C. C., Felsky, D., Remington, E., Wallace, T., Tong, R. P., Souza, R. P., Oh, G., Potkin, S. G., Lieberman, J. A., Meltzer, H. Y., & Kennedy, J. L. (2012). Dopamine D4 and D5 receptor gene variant effects on clozapine response in schizophrenia: Replication and exploration. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 37(1), 62-75. https://doi.org/10.1016/j.pnpbp.2011.11.018