Genetic Susceptibility to Periodontitis.

Periodontitis is a widespread inflammatory disease of the oral cavity that is influenced by genetic and environmental factors. Periodontitis has a high heritability, and particularly severe periodontitis often manifests before the age of 40, suggesting a strong genetic component. Genetic research has identified genetic variants associated with susceptibility to periodontitis that provide insights into the underlying mechanisms, which may improve future diagnostic and treatment strategies. We screened potential risk single-nucleotide variants (SNVs) identified in genetic association studies on periodontitis using the following selection criteria: genome-wide significance (p ≤ 5 × 10^-8) or suggestive significance (p ≤ 5 × 10^-6) with replication in ≥ 1 independent study. Additionally, we included SNVs with p < 5 × 10^-4 and ≥ 2 independent replications and functional validation. Due to the polygenic nature of periodontitis, we prioritized common variants with a minor allele frequency ≥ 1% and included rare variants (MAF ≤ 0.001) identified in whole-exome sequencing studies of severe cases with early onset. These criteria increased the reliability of identifying true genetic risk factors. The identified genetic risk loci for periodontitis can be primarily attributed to two biological functions: immune response and tissue integrity including regeneration. Genes such as SIGLEC5, DEFA1, FCERG1, PPBP/CXCL5/PF4, CDKN2B-AS1, and CTSC have a known function in neutrophil activity, antimicrobial defense, and mediation of the immune response. In particular, SIGLEC5, PLG, RSPO4, ROBO2, HMCN2, and CTSC appear to contribute to wound healing, extracellular matrix remodeling, and hemostasis. In particular, SIGLEC5, PLG, and PPBP/PF4 interact at the interface of immune function and tissue repair. In conclusion, risk genes for periodontitis point to the importance of the interplay between immune response and tissue homeostasis in the etiology of periodontitis. Future large-scale genome-wide association studies, whole-exome sequencing, and functional studies will likely uncover additional risk genes and refine our understanding of genetic contributions to periodontitis and help to develop potential therapeutic targets.