Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia.
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.
Shinkai
Takahiro
T
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
Müller
Daniel J
DJ
De Luca
Vincenzo
V
Shaikh
Sajid
S
Matsumoto
Chima
C
Hwang
Rudi
R
King
Nicole
N
Trakalo
Joseph
J
Potapova
Natalia
N
Zai
Gwyneth
G
Hori
Hiroko
H
Ohmori
Osamu
O
Meltzer
Herbert Y
HY
Nakamura
Jun
J
Kennedy
James L
JL
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
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