Association study of the vesicular monoamine transporter gene SLC18A2 with tardive dyskinesia

Clement C. Zai, Arun K. Tiwari, Marina Mazzoco, Vincenzo de Luca, Daniel J. Müller, Sajid A. Shaikh, Falk W. Lohoff, Natalie Freeman, Aristotle N. Voineskos, Steven G. Potkin, Jeffrey A. Lieberman, Herbert Y. Meltzer, Gary Remington, James L. Kennedy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Tardive dyskinesia (TD) is an involuntary movement disorder that can occur in up to 25% of patients receiving long-term first-generation antipsychotic treatment. Its etiology is unclear, but family studies suggest that genetic factors play an important role in contributing to risk for TD. The vesicular monoamine transporter 2 (VMAT2) is an interesting candidate for genetic studies of TD because it regulates the release of neurotransmitters implicated in TD, including dopamine, serotonin, and GABA. VMAT2 is also a target of tetrabenazine, a drug used in the treatment of hyperkinetic movement disorders, including TD. We examined nine single-nucleotide polymorphisms (SNPs) in the SLC18A2 gene that encodes VMAT2 for association with TD in our sample of chronic schizophrenia patients (n=217). We found a number of SNPs to be nominally associated with TD occurrence and the Abnormal Involuntary Movement Scale (AIMS), including the rs2015586 marker which was previously found associated with TD in the CATIE sample (Tsai etal., 2010), as well as the rs363224 marker, with the low-expression AA genotype appearing to be protective against TD (p=0.005). We further found the rs363224 marker to interact with the putative functional D2 receptor rs6277 (C957T) polymorphism (p=0.001), supporting the dopamine hypothesis of TD. Pending further replication, VMAT2 may be considered a therapeutic target for the treatment and/or prevention of TD.

Original languageEnglish (US)
Pages (from-to)1760-1765
Number of pages6
JournalJournal of Psychiatric Research
Volume47
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • Pharmacogenetics
  • Schizophrenia
  • Tardive dyskinesia
  • Vesicular monoamine transporter 2 (VMAT2/SLC18A2)

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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