GENETIC AND IMMUNOLOGIC ASPECTS OF PERIODONTAL DISEASES

牙周疾病的遗传和免疫学方面

• 批准号: 6142033
• 负责人: HARVEY Allen SCHENKEIN
• 金额: $ 95.27万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6142033
• 关键词: bactericidal immunity; genetic susceptibility; human subject; periodontitis; periodontium disorder

Studies of genetic and immunologic aspects of periodontal diseases. The overall goal of the proposed research is to address significant questions in periodontology via an integrated approach that exploits investigator expertise in human genetics, immunology, and bacterial pathogenesis. The investigators participating in these projects have worked together successfully for many years and were most recently supported by a Periodontal Disease Research Center grant form NIDR. We now propose a series of projects tied together as a Program Project; we propose to support a Core facility that provides administrative, clinical, and biostatistical support to the other projects. Each project will rely upon the Core for support of its scientific goals. Four interrelated and integrated scientific projects are proposed. We have been studying genetic aspects of early-onset periodontal diseases (EOP) for several years and have identified a specific gene (IL-1 on chromosome 2q) and a chromosomal region (19q) involved in EOP susceptibility. Additional chromosomal regions are strongly suggested, providing a rationale for continuing and expanding these studies. Secondly, we have been studying antibody responses and immunoglobulin production in periodontitis patients; major findings have been the observations that serum IgG2 levels are a heritable trait, and that IgG2 serum concentrations are significantly higher in some EOP patients than in healthy individuals or AP patients. These observations form the foundation for 3 higher in some EOP patients than in healthy individuals or AP patients. These observations form the foundation for 3 additional projects. The contribution of cytokines, including Il-1 (which is involved in EOP susceptibility, and levels of which are genetically determined), and lipid mediators (including PGE2 and PAF) to IgG2 production will be examined. Further, the contribution of PAG regulatory enzyme PAG acetyl-hydrolase, which is produced in low concentrations by monocytes from LJP patients, will be studied, Additionally, we have discovered that IgG2 antibody levels against phosphorylcholine (PC) are elevated in patients with periodontal attachment loss compared to healthy subjects; this led us to the observations that anti-PC inhibits IgG2 production and that several plaque microorganisms associated with periodontal destruction (A. actinomycetemcomitans, F. nucleatum) and endocaritis (S. sanguis), may have PC. The significance of this a-PC antibody and oral bacterial PC will be examined, and genetic control of a-PC levels will be explored.

牙周病的遗传和免疫学方面的研究。拟议研究的总体目标是通过利用研究人员在人类遗传学、免疫学和细菌发病机制方面的专业知识的综合方法来解决牙周病学中的重大问题。参与这些项目的研究人员已经成功合作多年，最近得到了 NIDR 牙周病研究中心拨款的支持。我们现在提议将一系列项目捆绑在一起作为一个计划项目；我们建议支持一个核心设施，为其他项目提供行政、临床和生物统计支持。每个项目都将依赖核心来支持其科学目标。提出了四个相互关联和综合的科学项目。我们多年来一直在研究早发性牙周病 (EOP) 的遗传方面，并确定了与 EOP 易感性有关的特定基因（染色体 2q 上的 IL-1）和染色体区域 (19q)。强烈建议额外的染色体区域，为继续和扩大这些研究提供了理由。其次，我们一直在研究牙周炎患者的抗体反应和免疫球蛋白的产生；主要发现是观察到血清 IgG2 水平是一种遗传性状，并且一些 EOP 患者的 IgG2 血清浓度显着高于健康个体或 AP 患者。这些观察结果为某些 EOP 患者的 3 高于健康个体或 AP 患者奠定了基础。这些观察结果为另外 3 个项目奠定了基础。将检查细胞因子，包括 Il-1（与 EOP 易感性有关，其水平由基因决定）和脂质介质（包括 PGE2 和 PAF）对 IgG2 产生的贡献。此外，我们还将研究 LJP 患者的单核细胞产生的低浓度 PAG 调节酶 PAG 乙酰水解酶的贡献。此外，我们发现牙周附着患者中针对磷酸胆碱 (PC) 的 IgG2 抗体水平升高与健康受试者相比的损失；这使我们观察到抗 PC 会抑制 IgG2 的产生，并且与牙周破坏（A. actinomycetemcomitans、F. nucleatum）和心内膜炎（S. sanguis）相关的几种牙菌斑微生物可能患有 PC。我们将检查这种 a-PC 抗体和口腔细菌 PC 的重要性，并探索 a-PC 水平的遗传控制。