SCOPE: Localized Aggressive Periodontitis Susceptibility and Patterns of Disease Initiation in Families

For the past ten years, we have studied an underserved population of African-Americans diagnosed with an aggressive form of periodontal disease, known as localized aggressive periodontitis (LAP). LAP starts early in life, affects specific teeth, and has high occurrence in family members. LAP progresses at a rapid rate, leading to early tooth loss if left untreated. Through two cycles of NIH funding, we recruited cohorts of 190 LAP children, along with 106 healthy siblings of LAP patients and 210 unrelated controls, unveiling a hyper-inflammatory response to lipopolysaccharide (LPS) in these individuals and their family members, a few key nucleotide variants in inflammatory genes associated with the phenotype, and differentiated DNA methylation patterns in key genes at different stages of the disease. It is our goal in this proposal to expand our knowledge on the susceptibility of individuals at risk by including key additional genetic, epigenetic and inflammatory markers and clinical features of disease in an integrated framework for (a) discerning LAP from healthy controls and further defining mechanistic pathways of the disease and (b) predict LAP responders and non-responders in the at-risk population. Results from the study are expected to reveal the diagnostic and predictive potential of genetic, epigenetic and inflammatory response for periodontitis and treatment outcomes. This susceptibility profile can applied and be further validated in different cohorts of at-risk populations around the globe and could set the stage for the development of early risk factors for more the common, slow progressive forms of periodontitis, leading to early intervention and prevention of bone loss in ½ Americans, currently diagnosed with periodontitis. Additionally, further elucidating the mechanistic pathways of this disease could eventually shed light into the susceptibility of more common chronic systemic inflammatory diseases that affect high-risk populations, such as diabetes and cardiovascular diseases.