Oxidative stress in tardive dyskinesia: Genetic association study and meta-analysis of NADPH quinine oxidoreductase 1 (NQO1) and Superoxide dismutase 2 (SOD2, MnSOD) genes

Clement C. Zai, Arun K. Tiwari, Vincenzo Basile, Vincenzo de Luca, Daniel J. Müller, Aristotle N. Voineskos, Gary Remington, Herbert Y. Meltzer, Jeffrey A. Lieberman, Steven G. Potkin, James L. Kennedy*

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Introduction: Tardive dyskinesia (TD) is a potentially irreversible side effect of antipsychotic medication treatment that occurs in approximately 25% of chronically treated schizophrenia patients. Oxidative stress has been one of the proposed mechanisms influencing TD risk. Pae et al. (2004) originally reported a significant association between TD and the NADPH quinine oxidoreductase 1 (NQO1) gene Pro187Ser (C609T, rs1800566) polymorphism in Korean schizophrenia patients; however, subsequent studies have not consistently replicated these findings. Similarly, Hori et al. (2000) reported an association between TD and the Manganese superoxide dismutase SOD2 (MnSOD) gene Ala9Val (rs4880) polymorphism in a Japanese sample, but most research groups failed to replicate their positive findings. Aims: We investigated the role of the NQO1 polymorphism Pro187Ser and SOD2 (Ala9Val) in a group of well-characterized schizophrenia patients (N = 223) assessed for TD. We also performed a meta-analysis of all the previously published TD studies, including data from our sample, on these polymorphisms, Pro187Ser (N = 5 studies) and Ala9Val (N = 9 studies). Results: We did not observe a significant association of the Pro187Ser or Ala9Val polymorphism with TD occurrence or AIMS scores in our Caucasian and African American samples when analyzed independently. Meta-analysis did not reveal a significant association of the Pro187Ser/Ala9Val alleles or genotypes with TD occurrence. Conclusions: Neither the NQO1 Pro187Ser nor the SOD2 Ala9Val appear to play a major role in TD risk, although additional polymorphisms should be tested before the role of NQO1 and SOD2 in TD can be completely excluded.

Original languageEnglish (US)
Pages (from-to)50-56
Number of pages7
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume34
Issue number1
DOIs
StatePublished - Jan 20 2010

Keywords

  • Manganese Superoxide Dismutase (MnSOD SOD2)
  • NADPH quinine oxidoreductase 1 (NQO1)
  • Oxidative stress
  • Pharmacogenetics
  • Schizophrenia
  • Tardive dyskinesia (TD)

ASJC Scopus subject areas

  • Biological Psychiatry
  • Pharmacology

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