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
• 期刊代码：222_02785846
• 类别：med
• 出版时间：27 April, 2012
• 卷：37
• 期：1
• 页码：62-75
• 文件大小：3060 K

摘要

class="h4">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.

class="h4">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.

class="h4">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.

class="h4">Conclusions

Overall, these results suggest a possible minor contribution of DRD4 variants, but not DRD5 variants, towards the AP/CLZ response phenotype.