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

The Pharmacogenomics Journal volume 9, pages 168–174 (2009)Cite this article

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.

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Acknowledgements

We thank the Canadian Institute for Health Research (CIHR) MOP79525, CHIR postdoctoral fellowship to AKT the CR Younger Foundation, the Bebensee Foundation, the Prentiss Foundation and the Ritter Foundation for funding this study. CIHR, the CR Younger Foundation, the Bebensee Foundation, the Prentiss Foundation and the Ritter Foundation had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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  1. Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    C C Zai, A K Tiwari, V Basile, V De Luca, D J Müller, N King, A N Voineskos, G Remington & J L Kennedy

  2. Psychiatric Hospital, Vanderbilt University, Nashville, TN, USA

    H Y Meltzer

  3. Columbia University Medical Centre, New York State Psychiatric Institute, New York City, NY, USA

    J A Lieberman

  4. Brain Imaging Center, University of California, Irvine, CA, USA

    S G Potkin

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Correspondence to J L Kennedy.

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Zai, C., Tiwari, A., Basile, V. et al. Association study of tardive dyskinesia and five DRD4 polymorphisms in schizophrenia patients. Pharmacogenomics J 9, 168–174 (2009). https://doi.org/10.1038/tpj.2009.2

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