Inflammatory Cytokines as Mediators of the Association Between Obesity and Chronic Apical Periodontitis.

Abstract

Objective: To assess genetic associations thatsupporta plausible causal interpretation of the obesity-chronic apical periodontitis (CAP) relationship, and to screen mediators including inflammatory cytokines, immune cell profiles and gut microbiota.

Methods: Two-sample Mendelian randomization (MR) based on public obesity GWAS and FinnGen CAP data; two-step MR mediation analysis to validate mediation effects of inflammation, gut microbiota and immune cell phenotypes.

Results: An association between genetically elevated body mass index (BMI) and increased susceptibility to CAP (ukb-b-2303, OR = 1.298; 95% CI: 1.170-1.439;P= 7.521E-07; FDR = 9.025E-06) was identified, compatible with a plausible causal interpretation. To further characterize the underlying mechanisms, two-step MR mediation analyses were performed. Three inflammatory cytokines were identified as significant mediators of the BMI-CAP relationship: M-CSF levels (OR = 1.107; 95% CI: 1.027-1.193; P = 0.008; FDR = 0.016), IL-6 levels (OR = 1.158; 95% CI: 1.071-1.252; P = 2.476E-04; FDR = 0.001), and TNFSF12 levels (OR = 0.885; 95% CI: 0.819-0.955; P = 0.002; FDR = 0.005). However, gut microbiota traits and immune cell phenotypes showed no significant mediating effects on the BMI-CAP causal association.

Conclusions: This MR analysis identified a genetically predicted association between obesity and CAP that appears to be mediated, at least in part, by inflammatory cytokines, supportive of a potential causal interpretation. These findings suggest weight management may represent a plausible strategy for the prevention and management of CAP.