title: Association study between a functional glutathione S-transferase (GSTP1) gene polymorphism (Ile105Val) and tardive dyskinesia.
abstract: A possible role for oxidative stress in the pathophysiology of tardive dyskinesia (TD) has previously been proposed (reviewed in Andreassen and Jorgensen [O.A. Andreassen, H.A. Jorgensen, Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats Implications for tardive dyskinesia? Prog. Neurobiol. 61 (2000) 525-541]). Long-term administration of antipsychotics 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 functional polymorphism of the gene coding for human glutathione S-transferase P1 (GSTP1), an important antioxidant enzyme involved in the detoxification of ROS, was studied in 225 chronic treatment-refractory patients with schizophrenia. An isoleucine (Ile) to valine (Val) substitution at codon 105 (Ile105Val) in the GSTP1 gene was genotyped. No significant difference in total AIMS scores was found among patients in the three genotype groups (chi(2)=1.47, d.f.=2, p=0.48). Moreover, no significant differences in genotype (chi(2)=0.05, d.f.=2, p=0.98) or allele frequencies (chi(2)=0.00, d.f.=1, p=1.00) were observed between subjects with and without TD. Our results suggest that the GSTP1 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, Department of Psychiatry, University of Toronto, Ont., Canada M5T 1R8. shinkai@med.uoeh-u.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shinkai
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Rudi
authors.initials: R
authors.lastname: Hwang
authors.forename: Chima
authors.initials: C
authors.lastname: Matsumoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hori
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohmori
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase