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

Prog Neuropsychopharmacol Biol Psychiatry. 2012 Apr 27;37(1):62-75. doi: 10.1016/j.pnpbp.2011.11.018. Epub 2011 Dec 8.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / therapeutic use
  • Black People / genetics
  • Clozapine / therapeutic use*
  • Female
  • Genetic Variation / genetics*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Prospective Studies
  • Receptors, Dopamine D4 / genetics*
  • Receptors, Dopamine D5 / genetics*
  • Schizophrenia / drug therapy*
  • Schizophrenia / ethnology
  • Schizophrenia / genetics*
  • Treatment Outcome
  • White People / genetics

Substances

  • Antipsychotic Agents
  • Receptors, Dopamine D4
  • Receptors, Dopamine D5
  • Clozapine