The Association of GLT6D1 rs1537415 G Allele with Aggressive and Advanced Chronic Periodontitis: A Comprehensive Meta-Analysis

Objective: To evaluate the association of the GLT6D1 rs1537415 G allele with susceptibility to aggressive periodontitis (AgP) and advanced chronic periodontitis (Stage III/IV, Grade B or C) by synthesizing evidence from human genetic association studies. Materials and Methods: Following PRISMA guidelines, a systematic search was conducted in PubMed, Web of Science, and Scopus through December 2024. Eligible studies analyzed the rs1537415 polymorphism in patients with AgP or advanced chronic periodontitis versus healthy controls. Three studies (n = 1,969) were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity and publication bias were evaluated using Chi², I², funnel plots, and Egger’s test. Results: The meta-analysis demonstrated a significant association between the G allele and periodontitis (OR = 1.58; 95% CI: 1.28–1.95; p < 0.0001). Subgroup analysis confirmed consistent effects in European and Sudanese populations, while no significant association was detected in the Brazilian cohort. Functional evidence indicates the G allele impairs GATA-3 transcription factor binding, contributing to immune dysregulation. Conclusions: The GLT6D1 rs1537415 G allele is significantly associated with increased risk of severe periodontitis. It may serve as a useful genetic marker in precision periodontology. Further research in diverse populations is needed to confirm gene-environment interactions and strengthen clinical applicability.