Gaba transporter SLC6A11 gene polymorphism associated with tardive dyskinesia. (February 2014)

• Record Type: Journal Article
• Authors: Son, Woo-Young; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Kang, Seung-Gul; Park, Young-Min; Yang, Hee Jung; Choi, Jung-Eun; An, Hyonggin; Seo, Han-Kyu; Kim, Leen
• Is Part Of: Nordic journal of psychiatry. Volume 68:Number 2(2014)
• Page Start: 123
• Page End: 128
• Publication Date: 2014-02
• Subjects: GABA -- Polymorphism -- Tardive dyskinesia; Psychopharmacology -- Periodicals; Psychotherapy -- Periodicals; Psychiatry -- Periodicals; Psychiatry -- Scandinavia -- Periodicals; 616.89
• DOI: 10.3109/08039488.2013.780260
• Languages: English
• ISSNs: 0803-9488

Abstract

Abstract: Background: 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. Methods: 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. Results: 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, GABRG 3 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. Conclusion: These results suggest that GABA receptor signaling pathway was associated with the increased susceptibility to TD in Korean schizophrenic patients.