Association study between glutathione S-transferase GST-M1, GST-T1, and GST-P1 polymorphisms and tardive dyskinesia.
OBJECTIVE
Data from several studies suggest that oxidative stress may play a role in the pathophysiology of tardive dyskinesia (TD). Glutathione S-transferase (GST) enzymes play important roles in protecting cells against oxidative stress. In the present study, we investigated the hypothesis that polymorphisms in genes for these detoxifying enzymes can influence susceptibility to TD in patients with schizophrenia.


METHODS
The GST-M1, GST-T1, and GST-P1 loci were analyzed by polymerase chain reaction (PCR)-based methods in 83 schizophrenic patients with TD and 126 schizophrenic without TD who were matched for antipsychotic drug exposure and other relevant variables. The multifactor dimensionality reduction (MDR) approach was used to analyze gene-gene interactions.


RESULTS
There were no significant differences in the distributions of the GST-M1, GST-T1, and GST-P1 genotypes between the TD and non-TD groups (p > 0.05). However, in comparison of the severity of TD among genotypes using Poisson regression showed that Ile/Ile genotype of GST-P1 had higher AIMS score compared to Ile/Val + Val/Val genotypes (X(2) = 7.13, p = 0.008). MDR analysis did not show a significant interaction between the three GST gene variants and susceptibility to TD (p > 0.05).


CONCLUSIONS
These results suggest that GST gene polymorphisms do not confer increased susceptibility to TD in patients with schizophrenia but TD severity might be related with GST-P1 variants.
Kang
Seung-Gul
SG
Department of Psychiatry, Korea University College of Medicine, Seoul, South Korea.
Lee
Heon-Jeong
HJ
Choi
Jung-Eun
JE
An
Hyonggin
H
Rhee
MinKyu
M
Kim
Leen
L
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D016012:Poisson Distribution; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy*; D012720:Severity of Illness Index
D014150:Antipsychotic Agents; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1