Causal relationships between inflammatory factors and Periodontitis: A bidirectional Mendelian randomization study

Abstract

Abstract Objective Periodontitis, a inflammatory disease, has been associated with systemic inflammatory markers, including C-reactive protein (CRP). However, the causal links between these factors and periodontitis are unclear. This study aims to elucidate these causal relationships using a bidirectional Mendelian randomization (MR) approach. (MR-PRESSO) technique. Materials and Methods Materials and Methods: We utilized a two-way summary-level MR design, capitalizing on publicly available summary statistics from genome-wide association studies (GWAS) for periodontitis and 42 systemic inflammatory markers, including CRP. We selected robust, independent single nucleotide polymorphisms (SNPs) as instrumental variables and performed the inverse-variance weighted (IVW) method to analyze the Wald ratios for each genetic variant. To account for potential pleiotropic bias, sensitivity analyses were conducted using methods such as MR-Egger regression, weighted median strategies, and the MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) technique. Results Our analysis reveals that higher levels of IL-1β (IVW estimate odds ratio [ORIVW] per SD genetic cytokines alteration: 2.26; 95% confidence interval [CI]: 1.02 − 5.00; P = 0.05), IL-6 (0.54, 0.29 − 1.00; P = 0.05), and IL-9 (0.56, 0.32 − 0.98; P = 0.04) are associated with an increased susceptibility to periodontitis. In contrast, no significant relationship was found between CRP or any other systemic inflammatory markers and periodontitis. Conclusion Our analysis specifically identifies increased levels of IL-1β, IL-6, and IL-9 as significant risk factors for developing periodontitis. However, no substantial link was observed between CRP and other inflammatory markers studied, implying that the inflammatory pathway to periodontitis may be cytokine-specific. Clinical Relevance: Our study provides genetic evidence into the interplay between CRP, systemic inflammatory markers, and periodontitis. Treatment strategies aimed at specific inflammatory markers could hold potential for reducing the risk of periodontitis.