Comparison of Genetic and Epigenetic Profiles of Periodontitis According to the Presence of Type 2 Diabetes. Comparison of Genetic and Epigenetic Profiles of Periodontitis According to the Presence of Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) and periodontitis (PD) have intricate connections as chronic inflammatory diseases. While the immune response is a key factor that accounts for their association, the underlying mechanisms remain unclear. To gain a deeper understanding of the connection, we conducted research using a multi-omics approach. We generated whole genome and EPIC array data from the periodontium of PD patients with DM (PDDM) and without DM to confirm genetic and epigenetic changes. Independent bulk and single-cell RNA sequencing data were employed to verify the expression levels of hypo-methylated genes. We observed a gradual rise in C>T base substitutions and hypomethylation in PD and PDDM patients compared to healthy participants. Furthermore, specific genetic and epigenetic alterations were prominently associated with the Fc gamma receptor-mediated phagocytosis pathway. The upregulation of these genes was confirmed in both the periodontal tissues of PD patients and the pancreatic tissues of T2DM patients. Through single-cell RNA analysis of peripheral blood mononuclear cells, substantial upregulation of Fc gamma receptors and related genes was particularly identified in monocytes. Our findings suggest that targeting the Fc-gamma signaling pathway in monocytes holds promise as a potential treatment strategy for managing systemic complications associated with diabetes. Overall design: We aimed to profile methylome of gigival tissue from PD and PDDM patients.