Localized aggressive periodontitis (LAP) is a severe disease, which often leaves its victims with obvious, irreversible physical scarring. Susceptibility to this condition is up to fifteen times higher in African-American children than Caucasian children, but the reasons for this imbalance are completely unknown. Aggregation in families and this racial disparity indicate a strong genetic component to susceptibility but the molecular basis of this is presently undefined. This lack of understanding prevents the development of preventative measures and early treatment. This disease is known to have a major association with the bacterium Actinobacillus actinomycetemcomitans. Recent evidence including our preliminary data, indicate that genetic variation in those immune system genes used to respond to bacteria play a substantial role in the genetic susceptibility to LAP. The principal objective of this study is to identify genes which influence the occurrence of LAP in African-Americans. We propose to examine three independent but related groups of genes, each covering a complimentary aspect of human anti-bacterial defenses. First we shall examine opsonisation potential in neutrophils by genotyping the Fc-gamma genes. Second, we shall consider the genetic bias towards Th1 or Th2 responses in these patients and finally we shall use microarray analysis to define novel and hitherto unsuspected targets for future genetic and therapeutic studies. By integrating molecular immunogenetic techniques into a cross-sectional and longitudinal epidemiological study, it is our goal to ultimately develop a genetic susceptibility profile which can be used to identify children who are at risk from LAP. Additionally, the data harvested from these studies should allow earlier treatment of disease and enhance our understanding of the molecular mechanisms underlying the pathogenesis of LAP and other forms of periodontitis. ? ?
