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

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• 作者：Rudi Hwang^a ; ^{rudirudi@gmail.com} ; Arun K. Tiwari^a ; ^{arun_tiwari@camh.net} ; Clement C. Zai^a ; ^{clement_zai@camh.net} ; Daniel Felsky^a ; ^{daniel_felsky@camh.net} ; Eli Remington^a ; ^{elilucasremington@gmail.com} ; Tessa Wallace^a ; ^{tessa.wallace@mail.mcgill.ca} ; Ryan P. Tong^a ; ^{ryan.p.tong@gmail.com} ; Renan P. Souza^b ; ^{renanrps@yahoo.com.br} ; Gabriel Oh^c ; ^{gabriel_oh@camh.net} ; Steven G. Potkin^d ; ^{sgpotkin@uci.edu} ; Jeffrey A. Lieberman^e ; ^{jlieberman@pi.cpmc.columbia.edu} ; Herbert Y. Meltzer^f ; ^{herbert.meltzer@vanderbilt.edu} ; James L. Kennedy^a
• 关键词：ABI ; Applied Biosystems ; ADHD ; attention deficit hyperactivity disorder ; ANCOVA ; Analysis of Covariance ; AP ; antipsychotic ; bp ; basepair ; BNEG ; Brief Psychiatric Rating Scale negative symptom subscale ; BPOS ; Brief Psychiatric Rating Scale positive symptom
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：2012
• 出版时间：27 April, 2012
• 年：2012
• 卷：37
• 期：1
• 页码：62-75
• 全文大小：3060 K

文摘

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.