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


OBJECTIVE
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.
Neurogenetics Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8.
Clement C
CC
Zai
Arun K
AK
Tiwari
Vincenzo
V
Basile
Vincenzo
V
de Luca
Daniel J
DJ
Müller
Aristotle N
AN
Voineskos
Gary
G
Remington
Herbert Y
HY
Meltzer
Jeffrey A
JA
Lieberman
Steven G
SG
Potkin
James L
JL
Kennedy
D000328:Adult; D017109:Akathisia, Drug-Induced / Q000235:genetics* / Q000503:physiopathology*; D016009:Chi-Square Distribution; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D039781:PubMed / Q000706:statistics & numerical data; D013482:Superoxide Dismutase / Q000235:genetics*; D000099156:Superoxide Dismutase 2
D016660:NAD(P)H Dehydrogenase (Quinone); D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C447479:NQO1 protein, human