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Nord J Psychiatry. 2014 Feb;68(2):123-8. doi: 10.3109/08039488.2013.780260. Epub 2013 Jun 24.

Gaba transporter SLC6A11 gene polymorphism associated with tardive dyskinesia.

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Woo-Young Son, Department of Psychiatry, Korea University College of Medicine , Seoul , South Korea , and Department of Biology, Cornell University College of Arts and Sciences , NY 14850 , USA.



Gamma-aminobutyric acid (GABA) insufficiency has been reported to be related to the tardive dyskinesia (TD) susceptibility. Inada et al. (Pharmacogenet Genomics 2008;18:317-23) identified eight genes belonging to GABA receptor signaling pathway that may be involved in TD susceptibility by genome-wide screening and they replicated associations in an independent sample for polymorphisms in SLC6A11 (GABA transporter 3), GABRG3 (c-3 subunit of GABA-A receptor) and GABRB2 (β-2 subunit of GABA-A receptor). In this study, we tried to replicate their finding in a larger Korean sample and find if any of the genes was associated with the susceptibility to TD.


We selected three polymorphisms in SLC6A11 (rs4684742), GABRG3 (rs2061051) and GABRB2 (rs918528) from the previous study. We carried out a case-control study (105 TD and 175 non-TD schizophrenic patients) to identify the association between the three candidate polymorphisms and susceptibility to TD and their epistatic interactions by using the multifactor dimensionality reduction (MDR) algorithm.


Among the three variants, SCL6A11 genotypes distribution showed a significant difference between the TD and non-TD patients (P = 0.049). However, GABRG3 and GABRB2 genotype distributions were not associated with TD (P = 0.268 and P = 0.976, respectively). Further, our analyses provided significant evidence for gene-gene interactions (SCL6A11, GABRG3 and GABRB2) in the development of TD. The odds ratio increased to 2.53 (CI = 1.515-4.217, P = 0.0003) when the genetic susceptibility to TD was analyzed with the three genes considered altogether through MDR approach.


These results suggest that GABA receptor signaling pathway was associated with the increased susceptibility to TD in Korean schizophrenic patients.

[Indexed for MEDLINE]

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