title: Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia.
abstract: 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.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, Clarke Division, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada, M5T 1R8. shinkai@med.uoeh-u.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shinkai
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Sajid
authors.initials: S
authors.lastname: Shaikh
authors.forename: Chima
authors.initials: C
authors.lastname: Matsumoto
authors.forename: Rudi
authors.initials: R
authors.lastname: Hwang
authors.forename: Nicole
authors.initials: N
authors.lastname: King
authors.forename: Joseph
authors.initials: J
authors.lastname: Trakalo
authors.forename: Natalia
authors.initials: N
authors.lastname: Potapova
authors.forename: Gwyneth
authors.initials: G
authors.lastname: Zai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hori
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohmori
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects; D004151:Dipeptides / Q000235:genetics*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D017382:Reactive Oxygen Species; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D014150:Antipsychotic Agents; D004151:Dipeptides; D005609:Free Radicals; D017382:Reactive Oxygen Species; C018170:prolylleucine; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human