Genomewide association studies in peri-implant bone loss

Project Summary/Abstract: Dental implants revolutionized dentistry. Unfortunately, implants have complications over time, including peri- implantitis (PI). PI affects 45% of patients who received dental implants, with 14.5% of the patients having moderate to severe PI. To date the pathophysiology of PI is not completely understood and PI resolution, after

treatment, is only observed in approximately 50% of implants. Given that more than 5 million implants are placed in the US per year, and that the prevalence of implants is expected to increase to 23% in 2026, PI is a significant clinical concern that needs to be addressed for optimal patient outcomes. PI shares similar characteristics with

periodontitis however, PI progresses more aggressively and ultimately leads to implant loss. Furthermore, even though these two conditions share common risk factors, including host/genetic influences, the role of genetics in PI is largely unknown. Understanding the genetic underpinnings on the prevalence and treatment outcomes of

PI is essential to the millions of people considering or currently treated with dental implants. Our long-term goal is to identify genetic traits that correlate with peri-implant bone loss and to discern the signaling cascades that underlie disease pathophysiology. Our objective here is to perform Genome-Wide Association Studies (GWAS)

to identify traits involved in peri-implant bone loss utilizing a mouse model (Hybrid Mouse Diversity Panel-HMDP). Our central hypothesis is that quantitative train loci (QTLs) associate with PI susceptibility and provide insight on appropriate treatment strategies. Our hypothesis is formulated on our preliminary studies using a ligature-

induced peri-implant bone loss model in three mouse strains (A/J, C3H/HeJ and C57BL/6J). Through µ-CT analysis, we observed statistically significant strain-dependent bone loss around dental implants, supporting a significant role of the genetic framework in ligature-induced peri-implant bone loss. We elected to use a mouse

model because clinical genetic studies pose significant challenges due to the complex and heterogeneous genetic make-up of patients and difficulties in controlling environmental factors. Since humans and mice share similar structural, functional and genetic traits, a mouse model would be effective for GWAS where controlling

the genetic and environmental framework is critical. The HMDP panel consists of more than 100 commercially available inbred mouse strains selected for systematic genetic analyses. This panel has been validated for many conditions including diabetes, cardiovascular disease and periodontitis. We plan to test our central hypothesis

and accomplish the objective of this study with the following specific aim to perform GWAS of ligature-induced peri-implant bone loss in the HMDP. We have developed the necessary expertise for the successful execution of the proposal. Completion of these studies will facilitate a new understanding of PI susceptibility, prognosis,

treatment and will reveal mechanistic differences between PI vs. periodontitis. Our success will significantly contribute to the NIH mission and positively impact science and health care and provide valuable information for a more comprehensive research proposal.