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

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.