Genetic and Epigenetic Factors Drive Periodontitis Susceptibility and Influence Treatment Outcomes

Periodontitis (PD) is a complex inflammatory condition affecting tooth-supporting tissues, primarily initiated by microbial biofilms but significantly influenced by host immune responses and genetic predisposition. Current standard-of-care often addresses the microbial component but struggles with the variability in disease progression and treatment outcomes due to individual host factors. Understanding the interplay of genetic and epigenetic factors, such as specific IL-1 polymorphisms or DNA methylation patterns, is crucial for unraveling disease susceptibility, predicting progression, and developing more personalized, effective therapeutic strategies beyond conventional approaches.

This comprehensive review synthesized existing literature on the genetic and epigenetic underpinnings of periodontitis. Researchers explored studies focusing on genetic polymorphisms related to inflammatory mediators, immune responses, antimicrobial peptides, matrix metalloproteinases (MMPs), and vitamin D receptor (VDR) pathways. Epigenetic mechanisms, including DNA methylation, histone modifications, non-coding RNAs, and emerging RNA methylation pathways, were also examined for their roles in modulating inflammation, tissue destruction, bone metabolism, and host-microbe interactions. The review also considered advances in transcriptomic technologies like RNA sequencing for biomarker identification.

The review highlighted that genetic polymorphisms significantly influence susceptibility to periodontitis, its progression, and treatment outcomes, particularly in genes associated with inflammatory mediators and immune responses. Key epigenetic mechanisms, such as DNA methylation and histone modifications, were found to modulate inflammation and tissue destruction, while non-coding RNAs play roles in bone metabolism and host-microbe interactions. Advances in RNA sequencing have enhanced the identification of molecular biomarkers and cell-specific gene expression profiles linked to disease severity and treatment responses. The integration of these factors suggests a path toward precision periodontology. > The potential for leveraging genetic and epigenetic profiling presents an exciting avenue for personalized periodontal care, including the use of epigenetic therapies targeting pathways involved in inflammation and tissue regeneration.