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

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Hwang R, Tiwari AK, Zai CC, Felsky D, Remington E, Wallace T, Tong RP, Souza RP, Oh G, Potkin SG, Lieberman JA, Meltzer HY, Kennedy JL

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.

PubMed ID

22203087 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Clozapine	Dopamine D5 receptor	Protein	Humans	Unknown	Binder	Details