How Genetics and Epigenetics Shape Periodontal Disease

A new review published in the Biomolecules and Biomedicine journal sheds light on how genetics and epigenetics shape the development of periodontitis, a chronic inflammatory disease that can lead to tooth loss. While bacteria play a key role in the disease, this study argues that genetic and epigenetic factors—especially DNA methylation are pivotal in understanding why some individuals develop more severe forms of periodontal disease than others.

Periodontitis affects millions globally and is a leading cause of tooth loss, yet its exact causes remain complex. The review emphasizes that periodontitis is polygenic, meaning many genetic factors combine with environmental and lifestyle influences to shape the severity of the disease.

The Role of Genetics and Epigenetics

Recent advances in genetic research have identified several new genetic loci linked to periodontitis, including MTND1P5 and SHISA9. These discoveries open new avenues for understanding the genetic risk factors that contribute to disease susceptibility. However, genes alone do not explain the full spectrum of periodontal disease.

Epigenetics changes in gene expression, not due to alterations in the DNA sequence, emerge as a crucial factor. The review highlights the role of DNA methylation, histone modifications, and non-coding RNAs in regulating immune responses and tissue repair in the gums. For example, exposure to bacterial infection can lead to methylation changes in genes such as RUNX2, which is involved in bone formation, linking microbial signals to impaired tissue repair and disease progression.

Key Findings: Genetic and Epigenetic Insights

• New Genetic Loci: The identification of new genetic risk loci, including MTND1P5 and SHISA9, furthers our understanding of the genetic basis of periodontitis and how they may contribute to disease susceptibility.
  

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  Epigenetic Regulation of Inflammation: DNA methylation and histone modifications influence inflammatory pathways in the gums, helping to explain the variation in tissue damage and healing across individuals.
  
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  Non-Coding RNAs as Potential Biomarkers: Non-coding RNAs like miR-146a are shown to be differentially expressed in periodontitis and correlate with key inflammatory markers such as TNF-α and IL-6. These molecules hold promise as potential biomarkers for both diagnosis and treatment monitoring.
  

Environmental Factors and Their Impact

Lifestyle factors, particularly smoking, significantly influence epigenetic changes that contribute to more severe forms of periodontitis. Smoking alters DNA methylation patterns in genes like TLR2 and TLR4, which are linked to immune response and tissue damage. Additionally, nutritional factors such as folate intake may also impact DNA methylation and influence disease progression, further underscoring the role of the environment in shaping disease outcomes.

Advancing Early Detection and Treatment

Two promising categories of biomarkers have emerged from this research:

• Protein Markers: Enzymes like MMP-8, which are involved in tissue breakdown, and myeloperoxidase (MPO), a marker of inflammation, show strong potential for distinguishing between healthy and diseased gum tissues. MMP-8, in its active form (aMMP-8), is already being explored for use in point-of-care testing for periodontitis.
  

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  RNA Markers: Changes in microRNA profiles, especially in saliva and gingival crevicular fluid, could serve as non-invasive biomarkers for diagnosing and monitoring periodontitis. Specific miRNAs like miR-381-3p and miR-143-3p have shown a correlation with disease severity.
  

Despite the promise of these biomarkers, further research is needed to standardize testing procedures and validate their use across diverse populations.

Looking Ahead: Multi-Omics and Personalized Medicine

The future of periodontal disease research lies in integrating multi-omics approaches, which combine genomics, methylomics, transcriptomics, proteomics, and metabolomics. These integrative methods will help to further clarify how the disease progresses, improve early detection, and enable more personalized treatment strategies for patients.

By incorporating molecular data alongside clinical findings, the field is moving toward precision medicine, where care is tailored to the individual's specific genetic and epigenetic risk factors.

Research Implications and Future Directions

• Gene and Epigenetic Interactions: New genetic loci such as MTND1P5 and SHISA9, along with epigenetic modifications, provide exciting new targets for future studies on periodontitis. Understanding the links between genetic variants, methylation changes, and gene expression in gum tissues will be critical to advancing treatment options.
  

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  Epigenetics in Specific Cells: The review emphasizes the importance of studying tissue- and cell-specific epigenetic changes in periodontitis. Understanding these specific changes will help to pinpoint therapeutic targets and improve our understanding of disease mechanisms.
  
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  Host-Microbe Interactions: Bacterial products, including lipopolysaccharides, have been shown to alter DNA methylation patterns and affect genes involved in bone formation. Future research should focus on modeling these interactions in both lab and clinical settings to better understand their role in disease progression.
  
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  Biomarker Validation: While biomarkers like aMMP-8 and miRNAs show promise, further validation studies are needed to assess their utility across diverse populations and under standardized conditions.
  
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  Ethnic Diversity in Research: Large, diverse cohorts will be essential to confirm the genetic and epigenetic findings and ensure they are applicable to a wide range of populations.
  

Conclusion

This review underscores the growing importance of genetics and epigenetics in the development of periodontitis. The integration of new genetic loci and epigenetic markers offers exciting possibilities for more personalized approaches to diagnosing and treating gum disease. However, continued research is necessary to refine these tools and establish their clinical applications. As the field moves toward precision medicine, researchers hope to better understand how genetic and environmental factors interact to shape periodontal disease, ultimately improving patient care.

More information:

Elena Jovanova et al, The role of genome-wide DNA methylation and polymorphisms in periodontitis etiology: A narrative review. Biomol Biomed [Internet]. 2025 Jul. 3 [cited 2025 Dec. 4].

Available from: https://doi.org/10.17305/bb.2025.12646

Journal information: Biomolecules and Biomedicine

Provided by: Association of Basic Medical Sciences of FBIH

Provided by Association of Basic Medical Sciences of FBIH