Abstract
Background: Periodontitis is a prevalent inflammatory disease influenced by both genetic and environmental factors. Among genetic determinants, polymorphisms in oxidative stress-related genes—particularly GSTM1, GSTT1, and GSTP1 (rs1695)—have been suggested as contributors to disease susceptibility. This systematic review and meta-analysis aimed to evaluate the association between GSTM1, GSTT1, and GSTP1 (rs1695) gene polymorphisms and the risk of periodontitis. Methods: Following PRISMA 2020 guidelines, a comprehensive literature search was conducted in four databases (PubMed, Scopus, Web of Science, and Google Scholar) from inception to October 2025 for eligible case-control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using I² and Q test (with p-values), and publication bias was evaluated using Egger’s test and funnel plots. Evidence certainty was assessed with GRADE. Results: Seven studies with 1,525 participants were included. GSTM1-null polymorphism was significantly associated with periodontitis (OR = 2.94, 95% CI: 1.13–7.63, I2=93.5%), particularly in Asians, larger studies, and heavy smokers in subgroup analyses. GSTT1-null polymorphism showed no significant effect (OR = 0.64, 95% CI: 0.38–1.09, I2=69.7% ). Initial pooled analyses indicated significant associations across all GSTP1 (rs1695) genetic models; however, these associations were not robust and lost statistical significance after exclusion of one study deviating from Hardy–Weinberg equilibrium. No publication bias was detected. Conclusions: This meta-analysis supports a potential role for the GSTM1-null polymorphism in increasing susceptibility to periodontitis. Associations for GSTP1 (rs1695) were less consistent and sensitive to study quality, while the GSTT1-null polymorphism showed no clear effect. According to GRADE, the certainty of evidence was moderate for GSTM1 and low for GSTT1 and GSTP1; results are therefore suggestive and require confirmation in larger multi-ethnic studies.