Association study between glutathione S-transferase GST-M1, GST-T1, and GST-P1 polymorphisms and tardive dyskinesia

Objectives: 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 (X²=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.