Association of GSTM1, GSTT1, and GSTP1 Gene Polymorphisms With Susceptibility to Periodontitis: A Systematic Review and Meta-Analysis With Exploratory Analysis of Apical Periodontitis.

Background: Periodontitis is an inflammatory condition in which oxidative stress significantly contributes to tissue damage. Genetic polymorphisms in antioxidant enzymes, particularly glutathione S-transferases (GSTs; GSTM1, GSTT1, and GSTP1), may influence an individual's susceptibility to periodontal inflammatory conditions, including periodontitis and apical periodontitis (AP). However, prior studies have reported inconsistent results. Accordingly, this study evaluates the association between GST polymorphisms and periodontitis susceptibility, while also incorporating AP in an exploratory framework. Methods: Eight case-control studies were retrieved from PubMed, Scopus, and EBSCO. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using a random-effects model due to high heterogeneity. Subgroup analyses were conducted by genotype, disease type, and ethnicity, along with exploratory pooled analyses combining periodontitis and AP. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS). Results: Exploratory pooled analyses indicated that the GSTM1 null genotype was associated with increased risk (OR = 2.84, 95% CI: 1.07-7.56, Conclusions: GSTM1 and GSTT1 polymorphisms may contribute to susceptibility to oral inflammatory conditions, particularly AP, whereas the evidence for periodontitis remains inconclusive. The findings highlight the potential role of compromised antioxidant defenses in disease pathogenesis. These results must be interpreted with caution as there was considerable heterogeneity and a small number of studies. Larger studies are required to validate these findings and elucidate possible mechanisms.