Paria Motahari, Negin Neshanifard
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; the results are therefore suggestive and require confirmation in larger multi-ethnic studies.
INTRODUCTION: Periodontitis is a prevalent inflammatory disease influenced by both genetic and environmental factors. Among genetic determinants, polymorphisms in oxidative stress-related g e n e s - p a r t i c u l a r l y 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 tests (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. The GSTM1-null polymorphism was significantly associated with periodontitis (OR=2.94, 95% CI: 1.13-7.63, I2=93.5%) in subgroup analyses, particularly among Asians, in larger studies, and among heavy smokers. 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 a study that deviated from Hardy-Weinberg equilibrium. No publication bias was detected.
CONCLUSION: 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; the results are therefore suggestive and require confirmation in larger multi-ethnic studies.