Interleukin-1 Composite Genotype and Alveolar Bone Loss

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DESCRIPTION (provided by applicant): Nearly all adult men and women will experience the loss of a tooth sometime during the course of their lives, and the risk of losing multiple teeth increases with age. Alveolar bone loss, a predictor of tooth loss, may be influenced by host inflammatory response to bacterial challenge. Observations that elevated levels of inflammatory mediators are related to specific polymorphisms associated with the interleukin-1 gene cluster, and, in turn, that increased levels of inflammatory mediators are associated with greater advanced alveolar bone loss lead to the hypothesis to be addressed in this proposed study: Hypothesis: To determine whether alveolar bone loss and incidence of tooth loss are accelerated in dentate men who exhibit specific variants of the IL-1 gene cluster that have been linked to increased production of inflammatory mediators in response to bacterial challenge compared to men without this genotype. Subjects: This hypothesis will be tested on 678 dentate men for whom 15-year rates of alveolar bone loss have been previously determined and who are currently enrolled in the Dental Longitudinal Study component of the VA Normative Aging Study, an established cohort of men followed for up to 30 years with triennial oral and medical examinations. Available historical data: Change in alveolar bone loss at all interproximal sites has been measured from at least 6 sequential sets of full-mouth films per subject spanning a minimum of 15 years, which have been digitized with a computer-assisted image transformation technique. Measures of percent remaining bone and mean rates of alveolar bone loss are available. Data for tooth loss, clinical periodontal indices, medical status, smoking, alcohol, behavioral, and other parameters have also been collected over the same 15-year interval. Data to be newly acquired for this study: Allelic variants in the TaqI and ApaI polymorphisms of the IL-1 gene cluster will be determined with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) from mononuclear cells obtained from a blood draw collected during routine study examination. Plan: Mean rates of alveolar bone loss will be compared among the genotypes with analysis of covariance, controlling for important clinical oral measures and other factors that independently influence alveolar bone loss. The risk of tooth loss will be compared among the genotypes. Significance: The results of this study may be useful in identifying a genetic component to oral bone loss.