Identifying the Genetic Contribution in Periodontitis

Objectives: Periodontitis is an inflammatory disease of the supporting tissues of the teeth and affects 47.2% of the population over age 30. Although bacteria, such as Porphyromonas gingivalis (P.g.), play a central role in periodontitis pathogenesis, environmental and genetic factors greatly affect disease severity. Indeed, periodontitis is approximately 50% heritable. We hypothesize that exploring genetic determinants associated with sensitivity or resistance to periodontal bone loss will assist in early diagnosis and management of patients with periodontitis.

Objective: Identify genetic traits that correlate with inflammation-induced periodontal bone loss.
Methods: Periodontal bone loss was induced by P.g.-LPS injections utilizing 54-mouse-strains (n≥6/strain) of the Hybrid Mouse Diversity Panel (HMDP). Micro-CT to assess bone loss was followed by Efficient Mixed-Model Association (EMMA), to identify genomic loci. The classic inbred strains with the lowest (A/J) and highest (C57BL/6J) bone loss were further characterized through: a) microarray, b) in vivo osteoclast number, and c) immunohistochemistry for monocytes/macrophages (Cd11B) and T-cells (Cd3).
Results: We observed a 6-fold difference in bone loss between the lowest (AXB13/PgnJ) and highest (BXD84/RwwJ) strains. Additionally, heritability of periodontal bone loss was 49%. EMMA identified genes that have previously been implicated in periodontitis including Tlr9, Hmgb1, Egf, Cd22, Ccr4, and Irak3. We found additional genes associated with inflammation and regulation of T- and B-cells. C57BL/6J showed statistically significant more osteoclasts (p=.0292) after LPS injections compared to A/J. Ongoing studies suggest that Cd11B (monocytes/macrophages) and Cd3 (T-cells) expression is also greater in C57BL/6J compared to A/J.
Conclusions: Similar to humans, periodontitis appears to be heritable in mice. Moreover, we identified genes/loci that may be important for periodontal bone loss. Ongoing studies to characterize the complete HMDP will identify genetic determinants that contribute to periodontal bone loss. Our ultimate goal is to identify genetic polymorphisms that are linked with high risk for periodontitis in mice and humans.