GENETICS OF PERIODONTAL DISEASES: MOLECULAR PATHWAYS OF INFLAMMATION, FROM SUSCEPTIBILITY GENES TO PRECISION PERIODONTOLOGY

Abstract

Periodontitis is one of the most prevalent chronic inflammatory diseases affecting humans, involving more than a billion people worldwide and remaining a leading cause of tooth loss. The disease is triggered by a dysbiotic subgingival biofilm. Yet decades of twin, family, and genome-wide studies show that the tempo and severity of tissue destruction depend substantially on the host's inherited and epigenetically modulated inflammatory response. This review synthesises current knowledge of the genetic architecture of periodontitis, moving from the classical candidate-gene era - anchored in interleukin-1 (IL-1) gene-cluster polymorphisms and the Kornman composite genotype - through genome-wide association studies implicating tissue-maintenance genes (SIGLEC5, PLG, ROBO2, ABCA1, PF4, CTSC), to monogenic and syndromic forms such as Papillon-Lefèvre syndrome, leukocyte adhesion deficiency type I, and Down syndrome. We further discuss host-microbiome genetic interactions, DNA methylation, non-coding RNA, and the dual role of bacterial CRISPR-Cas systems as virulence regulators and prospective therapeutics. We appraise the translational trajectory of this knowledge: the limited clinical utility of single-gene susceptibility testing, the promise and constraints of polygenic risk scores, host modulation therapy, and the first successful gene-therapy trial for a monogenic periodontitis-associated immunodeficiency. A concluding discussion synthesises these findings into practical implications for clinicians and identifies priorities for future research. We argue that periodontal genetic susceptibility should be understood less as simple hyperinflammation and more as an impaired capacity of periodontal tissue to resolve inflammation and repair itself, a reframing with direct implications for precision periodontology.