Interleukin-1 Composite Genotype and Alveolar Bone Loss

Interleukin-1 复合基因型与牙槽骨丢失

• 批准号: 6790811
• 负责人: MARTHA E NUNN
• 金额: $ 8.08万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6790811
• 关键词: clinical research; dental alveolus; genetic susceptibility; genotype; human genetic material tag; human subject; immune response; immunogenetics; inflammation; interleukin 1; longitudinal human study; male; pathologic bone resorption; polymerase chain reaction; restriction fragment length polymorphism; single nucleotide polymorphism; tooth loss

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.

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失去一颗牙齿，失去多颗牙齿的风险随着年龄的增长而增加。牙槽骨丢失是牙齿丢失的预测因子，可能受到宿主对细菌攻击的炎症反应的影响。观察到炎症介质水平升高与白细胞介素-1基因簇相关的特定多态性相关，反过来，炎症介质水平升高与更严重的晚期牙槽骨丢失相关，这导致了本研究中要解决的假设： 假设：确定与无此基因型的男性相比，具有IL-1基因簇特异性变体的有齿男性的牙槽骨丢失和牙齿丢失的发生率是否加速，该基因簇与细菌挑战引起的炎症介质产生增加有关。 主题：这一假设将在678名有牙齿的男性中进行测试，这些男性的15年牙槽骨丢失率先前已经确定，并且目前正在参加VA规范老化研究的牙科纵向研究部分，这是一个建立的男性队列，随访长达30年，每三年进行一次口腔和医学检查。 可用的历史数据：在所有邻间部位的牙槽骨丢失的变化已被测量，从至少6个连续组的全口电影，每个主题跨越至少15年，已被数字化与计算机辅助图像转换技术。测量剩余骨的百分比和牙槽骨丢失的平均速率是可用的。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、饮酒、行为和其他参数的数据。 本研究新获得的数据：将采用聚合酶链反应限制性片段长度多态性（PCR-RFLP）从常规研究检查期间采集的血样中获得的单核细胞中确定IL-1基因簇TaqI和ApaI多态性的等位基因变体。计划：将通过协方差分析比较不同基因型的平均牙槽骨丢失率，控制重要的临床口腔指标和其他独立影响牙槽骨丢失的因素。牙齿脱落的风险将在基因型之间进行比较。 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。