Association study between a functional glutathione S-transferase (GSTP1) gene polymorphism (Ile105Val) and tardive dyskinesia

Takahiro Shinkai*, Vincenzo De Luca, Rudi Hwang, Chima Matsumoto, Hiroko Hori, Osamu Ohmori, Gary Remington, Herbert Y. Meltzer, Jeffrey A. Lieberman, Steven G. Potkin, Jun Nakamura, James L. Kennedy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

A possible role for oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in Andreassen and Jorgensen [O.A. Andreassen, H.A. Jorgensen, Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats Implications for tardive dyskinesia? Prog. Neurobiol. 61 (2000) 525-541]). Long-term administration of antipsychotics alters dopaminergic turnover, which results in increased formation of reactive oxygen species (ROS). This is hypothesized to lead to TD through neuronal toxicity as a consequence of oxidative stress. In the present study, the relationship between TD and a functional polymorphism of the gene coding for human glutathione S-transferase P1 (GSTP1), an important antioxidant enzyme involved in the detoxification of ROS, was studied in 225 chronic treatment-refractory patients with schizophrenia. An isoleucine (Ile) to valine (Val) substitution at codon 105 (Ile105Val) in the GSTP1 gene was genotyped. No significant difference in total AIMS scores was found among patients in the three genotype groups (χ2 = 1.47, d.f. = 2, p = 0.48). Moreover, no significant differences in genotype (χ2 = 0.05, d.f. = 2, p = 0.98) or allele frequencies (χ2 = 0.00, d.f. = 1, p = 1.00) were observed between subjects with and without TD. Our results suggest that the GSTP1 gene polymorphism does not confer increased susceptibility to TD, although further studies are warranted before a conclusion can be drawn.

Original languageEnglish (US)
Pages (from-to)116-120
Number of pages5
JournalNeuroscience Letters
Volume388
Issue number2
DOIs
StatePublished - Nov 11 2005

Keywords

  • Free radical
  • Genetics
  • Glutathione S-transferase
  • Oxidative stress
  • Polymorphism
  • Schizophrenia
  • Tardive dyskinesia

ASJC Scopus subject areas

  • Neuroscience(all)

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