Interleukin 6 and Interleukin 1β hypomethylation and overexpression are common features of apical periodontitis: A case-control study with gingival tissue as control

Objectives: Apical periodontitis is a periradicular tissue disorder that usually arises from infection by microorganisms in the root canal system resulting in local bone resorption. This usually involves the dysregulation of inflammatory mediators, which can be mediated by epigenetic mechanisms. Thus, the objective of this study was to evaluate Interleukin 6 (IL6) and Interleukin 1 beta (IL1 beta) and DNA methylation and gene expression levels in apical periodontitis. Methods: Gene expression was analyzed in 60 participants using quantitative polymerase chain reaction, while the methylation levels of IL6 and IL1 beta promoters were analyzed in 72 patients using pyrosequencing. All statistical analyzes were performed using the GraphPad Prism software version 8.0. The p value was considered statistically significant when < 0.05. Results: A significantly higher IL6 and IL1 beta expression levels were observed in cases relative to controls (fold-changes of 27.4 and 11.43, respectively, and p < 0.0001). By comparing the same groups, lower promoter methylation levels were observed for both genes in cases (methylation percentage delta relative to controls of 24.57% and 16.02%, respectively, and p < 0.0001). A significant inverse correlation between gene expression and promoter methylation was observed for both IL6 (p = 0.0002) and IL1 beta (p = 0.001). Neither IL6 expression nor promoter methylation were significantly associated with cases' age, smoking history, alcohol consumption history or sex. For IL1 beta, alcoholic cases showed lower methylation level relative to non-alcoholic cases (p = 0.01), while females showed higher methylation levels relative to males (p = 0.03). Conclusions: Our data suggest a role for DNA methylation in IL6 and IL1 beta upregulation in apical periodontitis.