DRD4 polymosphisms and tardive dyskinesia

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The Pharmacogenomics Journal advance online publication 24 February 2009; doi: 10.1038/tpj.2009.2

Association study of tardive dyskinesia and five DRD4 polymorphisms in schizophrenia patients

C C Zai¹, A K Tiwari¹, V Basile¹, V De Luca¹, D J Müller¹, N King¹, A N Voineskos¹, G Remington¹, H Y Meltzer², J A Lieberman³, S G Potkin⁴ and J L Kennedy¹

1. Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
2. Psychiatric Hospital, Vanderbilt University, Nashville, TN, USA
3. Columbia University Medical Centre, New York State Psychiatric Institute, New York City, NY, USA
4. Brain Imaging Center, University of California, Irvine, CA, USA

Correspondence: Dr JL Kennedy, Neurogenetics, Centre for Addiction and Mental Health, 250, College Street, R-30, Toronto, Ontario, Canada M5T 1R8. E-mail: James_Kennedy@camh.net

Received 23 September 2008; Revised 11 November 2008; Accepted 8 January 2009; Published online 24 February 2009.

Abstract

Tardive dyskinesia (TD) is a side effect of chronic antipsychotic medication exposure. Abnormalities in dopaminergic activity in the nigro-striatal system have been most often suggested to be involved because the agents that cause TD share in common potent antagonism of dopamine D₂ receptors (DRD2). Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD, with the most consistent findings being an association between TD and the Ser9Gly polymorphism of the DRD3 gene and the TaqIA site 3' of the DRD2 gene. The DRD4 gene codes for the third member of the D₂-like dopamine receptor family, and the variable number tandem-repeat polymorphism in exon 3 of DRD4 has been associated with TD. However, other polymorphisms have not been thoroughly examined. In this study, we investigated five polymorphisms spanning the DRD4 gene and their association with TD in our European Caucasian sample (N=171). Although the exon 3 variable number tandem repeat was not associated with TD, haplotypes consisting of four tag polymorphisms were associated with TD in males. This study suggests that DRD4 may be involved in TD in the Caucasian population, although further replication studies are needed.