Purpose: Several lines of evidence support the fact that the presence of oxidative stress plays an important role in the pathophysiological mechanisms of schizophrenia (SCZ). The glutathione peroxidases (GPXs) and glutathione S-transferases (GSTs) are the major antioxidant enzymes. Polymorphic variants of GPX  and GST  can affect the antioxidant activities of their encoded enzymes. This study explored the possible associations of the GSTA1  and GPX3  gene polymorphisms and schizophrenia in Chinese Han population.
Methods: DNA from 648 healthy controls and 617 schizophrenic patients was genotyped for single-nucleotide polymorphisms (SNPs) rs3957357 in GSTA1  and rs736775 in GPX3  using a PCR-LDR genotyping assay. The χ² test compared differences in genetic distributions between the two groups in a case–control study. The generalized multifactor dimensionality reduction (GMDR) was used to explore the interaction between the GSTA1 gene and the GPX3 gene on the risk of SCZ.
Results: Significant differences in allelic and genotypic frequencies of GSTA1  rs3957357 were present between SCZ and control groups (GSTA1  rs3957357 χ²=6.172, P =0.046 by genotype, χ²=5.847, P =0.016, odds ratio=1.329, 95% confidence interval=1.055–1.674 by allele). No significant differences in allelic or genotypic frequencies of GPX3  rs736775 were detected between cases and controls (GPX3  rs736775: χ²=2.058, P =0.357 by genotype, χ²=1.853, P =0.173, odds ratio=1.131, 95% confidence interval=0.953–1.342 by allele). Moreover, the GMDR model showed that the interaction between GSTA1  rs3957357 and GPX3  rs736775 was associated significantly with SCZ risk, P =0.0107.
Conclusion: Our results suggest that GSTA1  rs3957357 SNP has an effect on the risk of SCZ and the interaction between GSTA1  rs3957357 and GPX3  rs736775 may affect the development of SCZ in Chinese Han population. However, these results should be validated by replication in different populations with large sample sizes.
Keywords: oxidative stress, schizophrenia, glutathione peroxidase, glutathione S-transferase, gene polymorphism