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: Periodontitis is a multifactorial inflammatory disease with complex interactions between microbial, environmental, and genetic factors. Cyclooxygenase-2 (COX-2), a key enzyme in prostaglandin synthesis, plays a significant role in periodontal inflammation. Single nucleotide polymorphisms (SNPs) in the COX-2 gene—particularly -765G/C (rs20417) and -1195G/A (rs689466)—have been investigated for their potential association with periodontitis, but results remain inconsistent across populations. Objective: This meta-analysis aimed to assess the association between twoCOX-2 gene polymorphisms (-765G/C and -1195G/A) and diagnosis of periodontitis, using aggregated data from observational studies across diverse populations. Methods: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Seven case-control studies published between 2009 and 2023 were included, with data extracted on genotype distributions, odds ratios (ORs), and confidence intervals (CIs). Meta-analyses were performed under dominant genetic models. Heterogeneity and publication bias were evaluated using I² statistics and funnel plots, respectively. Results: The -765G/C polymorphism displayed a significant association with increased risk of CP (OR = 1.61, 95% CI: 1.12–2.32, p = 0.03), with no significant heterogeneity (I² = 0%). The -1195G/A variant demonstrated a borderline significant association (OR = 1.86, 95% CI: 1.00–3.43, p = 0.05), with moderate heterogeneity (I² = 35%). Funnel plot asymmetry suggested minimal publication bias for -765G/C, but possible small-study effects for -1195G/A. Conclusions: This meta-analysis supports a significant association between the COX-2 -765G/C polymorphism and presence of periodontitis, with suggestive evidence for the -1195G/A SNP.These findings suggest that COX-2 promoter polymorphisms may serve as potential biomarkers for individualized risk stratification and precision-based management of periodontitis.