Lack of Association between Glutathione S-Transferase-M1, -T1, and -P1 Polymorphisms and Olanzapine-Induced Weight Gain in Korean Schizophrenic Patients

OBJECTIVE: Oxidative stress may be an important pathogenic mechanism in the obesity and metabolic syndrome. The aims of this study was to assess the possible association between the oxidative stress related Glutathione S-Transferase genes (GST-M1, GST-T1, and GST-P1) variants and the olanzapine-induced weight gain in Korean schizophrenic patients. METHODS: We categorized 78 schizophrenic patients into two groups the more than 7% weight gain from baseline (weight gain ≥7%) and the less weight gain (weight gain <7%) groups according to weight change between before and after long-term olanzapine treatment (440±288 days). All participants were genotyped for the GST-M1, GST-T1 and GST-P1 genes. Differences in allele frequencies between cohorts with different body weight changes were evaluated by a chi-square analysis and Fisher's exact test. The multifactor dimensionality reduction (MDR) approach was used to analyze gene-gene interactions. RESULTS: Mean body weight gain was 5.42 kg. There was no difference in the null genotype distribution of GST-M1 and -T1 between subjects with body weight gain ≥7% compared to subjects with body weight gain <7% (p>0.05). No significant difference in GST-P1 genotype and allele frequencies were observed between the groups (p>0.05). MDR analysis did not show a significant interaction between the three GST gene variants and susceptibility to weight gain (p>0.05). CONCLUSION: These findings do not support a relationship between the genetic variants of three GST genes (GST-M1, -T1 and -P1) and weight gain in Korean schizophrenic patients receiving olanzapine treatment.