Epigenetic Regulation in the Pathogenesis of Periodontitis

Epigenetic modifications regulate gene activity in response to environmental and intrinsic factors, offering potential as reversible biomarkers and therapeutic targets. Their role in periodontitis, however, remains insufficiently defined. This review critically evaluates current evidence on epigenetic mechanisms in periodontitis, emphasizing methodological challenges such as cell-type heterogeneity, small sample sizes, and the detection of meaningful tissue-specific changes. Chronic inflammation and environmental exposures, notably tobacco smoke, induce stable, gene-specific DNA methylation changes in gingival tissues. Key epigenetic alterations have been identified in several genes such as CYP1B1, AHRR, ROBO2, and PTP4A3, which are implicated in detoxification, epithelial repair, and immune responses. These modifications are often cell-type-specific. Despite their biological relevance, most studies are limited by small cohorts and mixed-cell population analyses, complicating interpretation. DNA CpG methylation is the primary focus, given its chemical stability and established analytical platforms, while histone and RNA modifications remain understudied due to technical challenges. Epigenetic regulation appears to contribute to the pathogenesis of periodontitis, particularly in response to persistent environmental and inflammatory stimuli. However, clinical translation is constrained by methodological limitations. Future research must incorporate larger sample sizes, address cellular heterogeneity, and investigate the reversibility of epigenetic marks following periodontal therapy or elimination of harmful exposures. Advancing tissue-specific epigenetic profiling may enhance early detection, risk stratification, and personalized prevention strategies. Rigorous study designs and standardized methodologies will be essential to realizing the clinical potential of epigenetic research in periodontal disease.