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Increasing lines of evidence show that oxidative stress plays a role in the pathophysiological mechanisms of schizophrenia (SCZ). Polymorphic variants of oxidative stress-related candidate genes GPX1 and GST1 can affect the antioxidant activities of their encoded enzymes. Therefore, this study aimed to explore the association between the single nucleotide polymorphisms (SNPs) of GPX1 and GSTP1 and susceptibility to schizophrenia in the Chinese Han population. DNA from 323 healthy controls and 210 schizophrenic patients was genotyped for SNPs rs1050450 in GPX1 and rs1695 in GSTP1 using a predesigned TaqMan SNP genotyping assay. Differences in genetic distributions between cases and controls were compared using the χ-test. No significant differences in allelic or genotypic frequencies of GPX1 rs1050450 or GSTP1 rs1695 were detected between cases and controls (GPX1 rs1050450: χ=0.370, P=0.831 by genotype, χ=0.377, P=0.539, odds ratio=1.145, 95% confidence interval=0.743-1.766 by allele; GSTP1 rs1695: χ=1.537, P=0.464 by genotype, χ=1.623, P=0.203, odds ratio=0.813, 95% confidence interval=0.592-1.118 by allele). Our results suggest that GPX1 rs1050450 and GSTP1 rs1695 SNPs are unlikely to play a major role in the pathogenesis of schizophrenia in the Chinese Han population. However, these results should be validated by replication in larger and independent samples.

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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 χ 2 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 χ 2 =6.172, P=0.046 by genotype, χ 2 =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: χ 2 =2.058, P=0.357 by genotype, χ 2 =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 rs3957357and 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.