GENETIC AND IMMUNOLOGIC ASPECTS OF PERIODONTAL DISEASES

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Studies of genetic and immunologic aspects of periodontal diseases. The overall goal of the proposed research is to address significant questions in periodontology via an integrated approach that exploits investigator expertise in human genetics, immunology, and bacterial pathogenesis. The investigators participating in these projects have worked together successfully for many years and were most recently supported by a Periodontal Disease Research Center grant form NIDR. We now propose a series of projects tied together as a Program Project; we propose to support a Core facility that provides administrative, clinical, and biostatistical support to the other projects. Each project will rely upon the Core for support of its scientific goals. Four interrelated and integrated scientific projects are proposed. We have been studying genetic aspects of early-onset periodontal diseases (EOP) for several years and have identified a specific gene (IL-1 on chromosome 2q) and a chromosomal region (19q) involved in EOP susceptibility. Additional chromosomal regions are strongly suggested, providing a rationale for continuing and expanding these studies. Secondly, we have been studying antibody responses and immunoglobulin production in periodontitis patients; major findings have been the observations that serum IgG2 levels are a heritable trait, and that IgG2 serum concentrations are significantly higher in some EOP patients than in healthy individuals or AP patients. These observations form the foundation for 3 higher in some EOP patients than in healthy individuals or AP patients. These observations form the foundation for 3 additional projects. The contribution of cytokines, including Il-1 (which is involved in EOP susceptibility, and levels of which are genetically determined), and lipid mediators (including PGE2 and PAF) to IgG2 production will be examined. Further, the contribution of PAG regulatory enzyme PAG acetyl-hydrolase, which is produced in low concentrations by monocytes from LJP patients, will be studied, Additionally, we have discovered that IgG2 antibody levels against phosphorylcholine (PC) are elevated in patients with periodontal attachment loss compared to healthy subjects; this led us to the observations that anti-PC inhibits IgG2 production and that several plaque microorganisms associated with periodontal destruction (A. actinomycetemcomitans, F. nucleatum) and endocaritis (S. sanguis), may have PC. The significance of this a-PC antibody and oral bacterial PC will be examined, and genetic control of a-PC levels will be explored.