Interleukin 6 and Interleukin 1ß 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 1ß (IL1ß) 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 IL1ß 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 IL1ß 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 IL1ß (p = 0.001). Neither IL6 expression nor promoter methylation were significantly associated with cases' age, smoking history, alcohol consumption history or sex. For IL1ß, 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 IL1ß upregulation in apical periodontitis.

Association of DNA sequence-independent genetic regulatory mechanisms with apical periodontitis: A scoping review.

OBJECTIVE: Different studies in the last decade have proposed that gene expression alterations that are independent of the DNA sequence may also play an important role in periapical disease. The present study aimed to assess the available evidence supporting a relationship between these alterations and apical periodontitis through a scoping review. DESIGN: Specific strategies were developed for different databases (MEDLINE via PubMed, Cochrane Library, Scopus, Web of Science, and Virtual Health Library) and a search performed by March 1st, 2019. The evidence sources were selected according to the eligibility criteria and underwent a critical appraisal of methodological quality. RESULTS: The initial search retrieved 212 references, with eight eligible articles after the removal of replicates and application of exclusion criteria. Five studies identified altered DNA methylation on inflammatory response genes (FOXP3, CXCL3, FADD, MMP2, MMP9, IFNG, IL4, IL12) on AP patients. Three others identified the alterations on the expression of several microRNAs (miR-29b, 106b, 125b, 143, 146a, 155, 198) during AP. No evidence was identified regarding mechanisms of histone methylation, or of epigenetic heritability or stability. CONCLUSIONS: There is available evidence for the involvement of different genetic regulatory mechanisms independent of changes in DNA sequence in the development or severity of apical periodontitis. However, due to methodological limitations, further research must be performed before novel therapies and diagnostic tools for AP may arise from these data.