Glutathione S-Transferase M1/T1 Polymorphisms and Schizophrenia Risk: A New Method for Quality Assessment and a Systematic Review

Background: GST genes were reported to be involved in susceptibility to mental disorder. The results between deletions of GST genes and schizophrenia were inconclusive and confusing. Therefore, we performed this updated meta-analysis to outline the association using a new method for quality assessment.Methods: Sixteen reported studies were selected, and the overall OR and 95% CI were calculated and analyzed by Review Manager 5.4 and STATE 12. The Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control studies was rewritten to evaluate the quality of published studies, as there was no Exposure in these studies and other factors should be suggested to assess the quality.Results: There was no significant association between deletions of GST genes and SZ risk (p > 0.05 in Random model). We also failed to find a significant relation between null genotypes and SZ risk in East Asian population. Based on further analysis of PCR methods, GSTM1 null was weakly associated with SZ risk in 8 studies using multiplex PCR (OR = 1.17, 95% CI = 1.00-1.37, p = 0.05), but GSTT1 null was a protective factor for SZ risk (OR = 0.73, 95% CI = 0.56-0.94, p = 0.02). When stratified by rewritten NOS stars and deductions, GSTM1 null was significantly associated with SZ risk in 9 studies with high quality (OR = 1.24, 95% CI = 1.08-1.43, p = 0.002), and in 10 studies with no deductions (OR = 1.20, 95% CI = 1.05-1.38, p = 0.007).Conclusion: GSTM1 null genotype may be a genetic risk factor for SZ in studies using multiplex PCR and high-quality studies. However, GSTT1 null might be a protective factor. Besides, we provided a new method for quality assessment and it was useful and should be promoted in further analysis.

Automated summary

This study conducted a meta-analysis to investigate the association between GST gene deletions and susceptibility to mental disorder. The results suggested that GSTM1 null genotype may be a genetic risk factor for schizophrenia, while GSTT1 null genotype may have a protective effect. Additionally, the study proposed a new method for quality assessment, which could be valuable for future analyses.