Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia

Takahiro Shinkai*, Daniel J. Müller, Vincenzo De Luca, Sajid Shaikh, Chima Matsumoto, Rudi Hwang, Nicole King, Joseph Trakalo, Natalia Potapova, Gwyneth Zai, Hiroko Hori, Osamu Ohmori, Herbert Y. Meltzer, Jun Nakamura, James L. Kennedy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


A possible involvement of oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in [Andreassen, O.A., Jorgensen, H.A., 2000. Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats. Implications for tardive dyskinesia? Progress in Neurobiology 61, 525-541.]). Long-term administration of neuroleptics 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 possible functional polymorphism of the human glutathione peroxidase (GPX1) gene (an important antioxidant enzyme) was studied in 68 chronic treatment-refractory patients with schizophrenia. A proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) in the GPX1 gene was genotyped. No significant difference in total Abnormal Involuntary Movements Scale (AIMS) scores was observed among patients in the three genotype groups. Moreover, no significant differences in genotype or allele frequencies were observed between subjects with and without TD. Our results suggest that the GPX1 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)123-128
Number of pages6
JournalPsychiatry Research
Issue number2
StatePublished - Feb 28 2006


  • Free radical
  • Genetics
  • Glutathione peroxidase
  • Oxidative stress
  • Polymorphism
  • Schizophrenia
  • Tardive dyskinesia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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