Periodontal diseases, which are characterized by local inflammation affecting the supporting tissues surrounding the teeth, affect a large proportion of the population. In early onset periodontal diseases (EOP), which affect up to 2.5% of individuals in certain populations in the United States, there is rapid destruction of periodontal tissues in teenagers and young adults. The etiology and pathogenesis of these diseases are of great interest since they involve the interaction of local bacterial factors, unusual local and systemic host responses, and genetic risk factors. Furthermore, both the epidemiological distribution of the disease and a variety of host response variables are influenced by race. In this Periodontal Disease Research Center application we propose projects that explore immunologic, bacteriologic and genetic aspects of periodontal diseases with an emphasis on the early onset forms of disease. The proposed research projects will take advantage of and expand upon existing resources of the Virginia Commonwealth University Clinical Research Center for Periodontal Diseases, most notable of which are a large, well organized patient data base, a resource of over 225 families of subjects with EOP, a serum bank from over 1,000 periodontally characterized subjects, and a collection of DNA samples and immortalized cell lines from over 500 subjects in informative EOP families. We propose one Core for this Center (Project 9001), which functionally combines administrative, clinical, and biostatistical and data management support for the research projects. In Project 1 (Molecular Genetic Studies of Early Onset Periodontitis), studies will be carried out that seek to determine the underlying genetic basis for predisposition of EOP. IN this study, which is based upon our preliminary data indicating the very high likelihood that risk for EOP is an autosomal dominant trait with high penetrance, we seek to identify some of the specific genes and the biochemical and physiological processes that underlie risk for EOP. In Project 2 (Immunologic Studies of Periodontitis), we propose to pursue compelling preliminary data that indicate that serum concentrations of IgG subclasses, particularly IgG2, are influenced both by periodontal diagnosis and by race. We will seek to determine the immunological basis for this observation by assessing patient response to carbohydrate antigens, by assessing the roles of T and B lymphocytes in production of subclass responses in cultures of patients' cells, and by determining the influence of periodontal therapy on immunoglobulin levels. In Project 3 (Molecular Biology of Porphyromonas gingivalis virulence) we will examine virulence factors of Porphyromonas gingivalis, an organism associated with both generalized forms of EOP and adult periodontitis. In preliminary studies we have cloned a protease gene from P. gingivalis in E. coli; this protease may be functionally important in the virulence of P. gingivalis since it degrades the complement protein C3 as well as other proteins. The gene for this protease, which will be characterized, will also be used as a probe to evaluate potential differences in various bacterial isolates from periodontal sites.
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