The broad objective of this proposal is to assess microbial risk factors for the initial periodontal lesion.
The specific aims will determine whether putative microbial risk markers for periodontal lesions could also be risk factors for initial lesions. Also, the association between the role of an altered interleukin-1 (IL-1) genotype, with increased expression of IL-1a and IL-1b in gingival crevicular fluid, and prevalence and progression of periodontitis will be determined. Reliable risk factors for initial lesions can then be used to identify susceptible individuals either before or in early phases of disease. Preventive intervention before tissue destruction occurs would be better, and less expensive, than treating diseased sites. Furthermore, if periodontal pathogens and mechanisms of pathogenesis of initial lesions could be defined, other research and treatment studies can be targeted to the appropriate species and mediators of tissue destruction. Putative pathogens and cytokines in 300 subjects will be examined using new molecular biology technologies for rapid assays of species, including new spirochete taxa, detection of cytokines and altered genotype for cytokine production.
Aim 1 examines the prevalence of subjects with microbial risk markers for periodontal loss or an altered IL-1 genotype, in a cross-sectional study comparing subjects with minimal periodontal attachment loss (cases) with periodontally healthy subjects (controls). The hypothesis to be tested is that the risk (or suspected) marker for periodontal attachment loss will be higher in cases than in healthy controls.
Aim 2 is a prospective cohort study monitoring 200 subjects selected from the first aim, to determine whether subjects with microbial risk markers for attachment loss or an altered IL-1 genotype demonstrate more extensive attachment loss than subjects without these risk markers. Subjects will undergo comprehensive clinical and microbial monitoring with measurements repeated at 6-month intervals for two years. Clinical characteristics of initial lesion subjects, including different patterns of attachment loss will be defined.
The third aim will evaluate site-specific associations of initial periodontal lesions and the cultivable subgingival microbiota, cultivated and uncultivated taxa of spirochetes, and cytokines IL-1a and IL-1b. Microbiologic, genetic and clinical information from this proposal will significantly advance understanding of the microbial etiology of initial periodontitis, which will have profound significance for basic studies in periodontal research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE009513-07
Application #
6176830
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Mangan, Dennis F
Project Start
1992-03-15
Project End
2003-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
7
Fiscal Year
2000
Total Cost
$751,081
Indirect Cost
Name
Forsyth Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02142
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Paster, Bruce J; Russell, Meaghan K; Alpagot, Tamer et al. (2002) Bacterial diversity in necrotizing ulcerative periodontitis in HIV-positive subjects. Ann Periodontol 7:8-16
Yang, E Y; Tanner, A C R; Milgrom, P et al. (2002) Periodontal pathogen detection in gingiva/tooth and tongue flora samples from 18- to 48-month-old children and periodontal status of their mothers. Oral Microbiol Immunol 17:55-9
Tanner, A C R; Milgrom, P M; Kent Jr, R et al. (2002) The microbiota of young children from tooth and tongue samples. J Dent Res 81:53-7
Tanner, A C R; Milgrom, P M; Kent Jr, R et al. (2002) Similarity of the oral microbiota of pre-school children with that of their caregivers in a population-based study. Oral Microbiol Immunol 17:379-87

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