Association between the null polymorphisms of GSTT1 and GSTM1 and the risk of gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND

The relationship between the null polymorphisms of the GSTT1 and GSTM1 genes and the risk of gestational diabetes mellitus has been previously investigated. However, these scattered evidence remained controversial. Therefore, this systematic review and meta-analysis was performed to synthesize previous findings and statistically estimate whether these polymorphic variants are associated with the risk of this common pregnancy complication.

METHODS

A systematic literature search was conducted in PubMed, Clarivate Web of Science, Elsevier Scopus, Cochrane Library, and EBSCOhost (from inception to February 28, 2025), using a predefined search strategy. The methodological quality of each study was assessed by using the Newcastle-Ottawa Scale (NOS). Pooled odds ratio (OR) and 95% confidence interval (95% CI) were estimated to measure the effect size. In addition, heterogeneity, sensitivity, and publication bias were also examined. All statistical tests were performed using the R language (version 4.4.2) and STATA software (version 14.2). This study followed the PRISMA 2020 statement, and the protocol was prospectively registered in PROSPERO (CRD420250621255).

RESULTS

For the deletion polymorphism of GSTT1, seven studies with 1012 cases and 1081 controls were integrated into the pooled estimation. For the null variant of GSTM1, seven datasets with 1012 diabetic and 1081 control individuals were included in the meta-analysis. Pooled estimates showed statistical significance for the null polymorphisms of GSTT1 (OR: 1.43, 95% CI: 1.08–1.89, P = 0.01) and GSTM1 (OR: 2.01, 95% CI: 1.68–2.39, P < 0.01). The symmetric funnel plot shape and statistical tests of publication bias suggested no substantial file drawer problem. However, the pooled estimates of the GSTT1 null polymorphism lost statistical significance in the leave-one-out sensitivity analysis and Galbraith plot-guided heterogeneity adjustment.

CONCLUSION

The results suggested that the null polymorphisms of GSTT1 and GSTM1 may be associated with an increased risk of gestational diabetes mellitus. Notably, the association for the GSTT1 null polymorphism was not robust and warrants further confirmation. CLINICAL TRIAL NUMBER: Not applicable.