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.
Zai
Clement C
CC
Neurogenetics Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8.
Tiwari
Arun K
AK
Basile
Vincenzo
V
de Luca
Vincenzo
V
Müller
Daniel J
DJ
Voineskos
Aristotle N
AN
Remington
Gary
G
Meltzer
Herbert Y
HY
Lieberman
Jeffrey A
JA
Potkin
Steven G
SG
Kennedy
James L
JL
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