Association of Single Nucleotide Polymorphisms in the Cyclooxygenase-2 (COX-2) Gene with Periodontal Disease-A Systematic Review with Meta-Analysis and Implications for Personalized Dentistry.

Background: Genetic polymorphisms in the cyclooxygenase-2 (COX-2) gene may contribute to individual susceptibility to periodontal disease. A meta-analysis assessed the association between three COX-2 single-nucleotide polymorphisms (SNPs) namely, -765 G/C (rs20417), -1195 G/A (rs689466), and 8473 T/C (rs5275), and the risk of CP. Methods: Following the PRISMA 2020 guidelines, we conducted a comprehensive search of five electronic databases and additional sources. The eligible studies were observational (case-control or cohort) with genotypic data comparing individuals with periodontal disease and periodontally healthy controls. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS), and the certainty of evidence was evaluated via the GRADE framework. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under dominant genetic models. Results: Seven studies (n = 1467 participants) met the inclusion criteria. No eligible studies evaluated the 8473 T/C SNP. The meta-analysis of the -765 G/C variant revealed a significant association with periodontal disease (OR = 1.61; 95% CI: 1.12-2.32, p = 0.03; I² = 0%). For the -1195 G/A variant, the pooled OR was 1.86 (95% CI: 1.00-3.43, p = 0.05; I² = 35%), suggesting a borderline significant association. The certainty of evidence was graded as moderate for -765 G/C and low for -1195 G/A. Conclusions: The COX-2 -765 G/C polymorphism is significantly associated with increased CP risk, while the -1195 G/A variant shows a potential, though less certain, link. Larger, high-quality studies using standardized classifications are needed to confirm these associations.