Association analysis of NAD(P)H∶quinone oxidoreductase (NQO1) Pro187Ser genetic polymorphism and tardive dyskinesia in patients with schizophrenia in Taiwan

Abstract

We read with interest a recent study by Pae and colleagues (Pae et al., 2004) regarding a genetic polymorphism Pro187Ser on the NAD(P)H:quinone oxidoreductase ( NQO1 ) gene being associated with tardive dyskinesia (TD). TD is an irregular, non-rhythmic involuntary movement disorder following long-term antipsychotic treatment. Although the pathogenesis of TD is not completely understood, one of the main hypotheses has been focused on neurodegeneration and cell damage in basal ganglia due to the generation of reactive oxygen species (ROS) (Elkashef and Wyatt, 1999; Lohr et al., 2003). NQO1 is a member of the phase II detoxification enzymes and has been suggested to play an important role in the cellular defence against oxidative stress (Ross et al., 2000). Previous studies have also indicated the expression of NQO1 in the substantia nigra, an essential region for movement control in humans (Drukarch and van Muiswinkel, 2000). Because of its expression in human brain and its antioxidant function, it is plausible that the genetic variants on the NQO1 gene that encode proteins with functional differences may be candidates for TD susceptibility. In the following study, we attempted to replicate the study by Pae et al. (2004) in a larger population regarding the association between NQO1 Pro187Ser polymorphism and TD. However, our results were discrepant with regard to the original report.