Interleukin-1 Composite Genotype and Alveolar Bone Loss

描述(由申请人提供)：几乎所有成年男性和女性都会在一生中的某个时候经历一颗牙齿的脱落，并且随着年龄的增长，失去多颗牙齿的风险会增加。牙槽骨丢失是牙齿脱落的一个预测指标，可能受到宿主对细菌攻击的炎症反应的影响。炎症介质水平的升高与白细胞介素1基因簇相关的特定多态性有关，反过来，炎症介质水平的升高与更严重的晚期牙槽骨丢失相关，这导致了这项拟议研究中要解决的假设： 假设：要确定与没有这种基因的男性相比，表现出IL-1基因簇特定变异的齿状男性是否会加速牙槽骨丢失和牙齿脱落的发生，这种变异与细菌攻击时炎性介质的产生增加有关。 研究对象：这一假设将在678名齿状男性身上进行测试，这些男性之前已经确定了15年的牙槽骨丢失率，目前正在参加退伍军人标准老龄化研究的牙科纵向研究部分，这是一个既定的男性队列，对其进行长达30年的跟踪调查，每三年进行一次口腔和医学检查。 可获得的历史数据：所有近端位置的牙槽骨丢失的变化是从每个受试者至少15年的至少6套连续全口片中测量出来的，这些照片已经用计算机辅助图像转换技术进行了数字化。可测量剩余骨量百分比和平均牙槽骨丢失率。在相同的15年时间间隔内，还收集了牙齿脱落、临床牙周指数、医疗状况、吸烟、酒精、行为和其他参数的数据。 本研究将获得的最新数据：IL-1基因簇TaqI和APAi多态的等位基因变异将通过聚合酶链式反应-限制性片段长度多态(PCR-RFLP)从常规研究检查中采集的血样中获得。计划：通过协方差分析，控制重要的临床口腔测量和其他独立影响牙槽骨丢失的因素，比较不同基因型之间的平均牙槽骨丢失率。牙齿脱落的风险将在不同的基因类型之间进行比较。 意义：这项研究的结果可能有助于确定口腔骨丢失的遗传成分。

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.