GABA transporter SLC6A11 gene polymorphism associated with tardive dyskinesia

Woo Young Son, Heon-Jeong Lee, Ho-Kyoung Yoon, Seung Gul Kang, Young Min Park, Hee Jung Yang, Jung Eun Choi, Hyonggin An, Han Kyu Seo, Leen Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)123-128
Number of pages6
JournalNordic Journal of Psychiatry
Volume68
Issue number2
DOIs
Publication statusPublished - 2014 Feb 1

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gamma-Aminobutyric Acid
GABA Receptors
Genes
Multifactor Dimensionality Reduction
Dyskinesias
Genotype
Tardive Dyskinesia
Genetic Predisposition to Disease
Genomics
Case-Control Studies
Odds Ratio
Genome

Keywords

  • GABA
  • Polymorphism
  • Tardive dyskinesia

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

GABA transporter SLC6A11 gene polymorphism associated with tardive dyskinesia. / 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.

In: Nordic Journal of Psychiatry, Vol. 68, No. 2, 01.02.2014, p. 123-128.

Research output: Contribution to journalArticle

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. / GABA transporter SLC6A11 gene polymorphism associated with tardive dyskinesia. In: Nordic Journal of Psychiatry. 2014 ; Vol. 68, No. 2. pp. 123-128.
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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, 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. Conclusion: These results suggest that GABA receptor signaling pathway was associated with the increased susceptibility to TD in Korean schizophrenic patients.",
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AU - Lee, Heon-Jeong

AU - Yoon, Ho-Kyoung

AU - Kang, Seung Gul

AU - Park, Young Min

AU - Yang, Hee Jung

AU - Choi, Jung Eun

AU - An, Hyonggin

AU - Seo, Han Kyu

AU - Kim, Leen

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

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