Localized juvenile periodontitis (LJP) is a destructive type of periodontal disease that affects 2% of the African American population. LJP segregates within certain families, and individuals within these families are at increased risk for disease. Formal genetic studies conclude that LJP is transmitted as an autosomal dominant trait, indicating that a gene of major effect is important in LJP disease etiology. Several subforms of juvenile periodontitis are known to exist and each may be genetically different. Functional and morphological abnormalities have been reported in peripheral blood neutrophils of a significant percentage of LJP patients. Also a specific bacteria, Actinobacillus actinomycetemcomitans has shown a significant association with LJP. Certain genotypes of this bacteria may selectively exploit an inherent neutrophil defect in susceptible individuals. The central hypothesis of this study is that increased risk for LJP is due to an inherited neutrophil defect in susceptible individuals.
The Aim of this study is to evaluate the role of several genetically controlled risk factors in LJP disease etiology. These include neutrophil receptors C5a, fMLP, and IL-8, as well as GP1 10, diacylglycerol kinase, annexin Ill and the vitamin D binding protein. Our study cohort will consist of 40 African American families (300 individuals) segregating for LJP. We will characterize these individuals for a number of disease presentation and host response variables including: clinical measures of periodontal tissue destruction, the presence of specific A. actinomycetemcomitans genotypes, and host immune response patterns including serum IgG response to A. actinomycetemcomitans and the density of neutrophil receptors (fMLP) and surface proteins (GP1 10) to assess heterogeneity in this African- American LJP population. We will then conduct linkage studies to evaluate the evidence for the role of specific neutrophil risk genes in the etiology of LjP in this population. Results will be assessed by calculation of pairwise logarithm of the odds (lod) scores to determine support for or against genetic linkage of each candidate marker to the LJP trait. Support for linkage will also be assessed using model free methods and will include formal analyses of heterogeneity. Systematic assessment of these candidate probes could ultimately provide positive risk markers with which to screen genetically susceptible populations at high risk for LJP, permitting early identification, diagnosis, and treatment.
| Hart, T C; Hart, P S; Bowden, D W et al. (1999) Mutations of the cathepsin C gene are responsible for Papillon-Lefevre syndrome. J Med Genet 36:881-7 |
| Mann, S S; Pettenati, M J; von Kap-herr, C et al. (1998) Reassignment of peptidyl prolyl isomerase-like 1 gene (PPIL1) to human chromosome region 6p21.1 by radiation hybrid mapping and fluorescence in situ hybridization. Cytogenet Cell Genet 83:228-9 |
| Hart, T C; Kornman, K S (1997) Genetic factors in the pathogenesis of periodontitis. Periodontol 2000 14:202-15 |
