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

摘要

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.