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

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 et al., 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.

• Authors: 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
• Journal: Journal of psychiatric research (J Psychiatr Res) Vol. 47 Issue 11 Pg. 1760-5 (Nov 2013) ISSN: 1879-1379 [Electronic] England
• PMID: 24018103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• RNA, Messenger
• SLC18A2 protein, human
• Vesicular Monoamine Transport Proteins

Topics

• Analysis of Variance
• Female
• Gene Frequency
• Genetic Association Studies
• Genotype
• Humans
• Male
• Movement Disorders (genetics)
• Polymorphism, Single Nucleotide (genetics)
• RNA, Messenger (metabolism)
• Vesicular Monoamine Transport Proteins (genetics, metabolism)