Immunogenetics and LAP susceptibility

免疫遗传学和 LAP 易感性

• 批准号: 6661914
• 负责人: GRANT GALLAGHER
• 金额: $ 19.44万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ DENTAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6661914
• 关键词: Actinobacillus actinomycetemcomitans; African American; adolescence (12-20); antibody receptor; bactericidal immunity; clinical research; gene environment interaction; genetic markers; genetic susceptibility; human subject; immunogenetics; microarray technology; opsonin; periodontitis; racial /ethnic difference

DESCRIPTION (provided by applicant): Localized aggressive periodontitis (LAP) is a severe disease, which often leaves its victims with obvious, irreversible physical scarring. Susceptibility to this condition is up to fifteen times higher in African-American children than Caucasian children, but the reasons for this imbalance are completely unknown. Aggregation in families and this racial disparity indicate a strong genetic component to susceptibility but the molecular basis of this is presently undefined. This lack of understanding prevents the development of preventative measures and early treatment. This disease is known to have a major association with the bacterium Actinobacillus actinomycetemcomitans. Recent evidence including our preliminary data, indicate that genetic variation in those immune system genes used to respond to bacteria play a substantial role in the genetic susceptibility to LAP. The principal objective of this study is to identify genes which influence the occurrence of LAP in African-Americans. We propose to examine three independent but related groups of genes, each covering a complimentary aspect of human anti-bacterial defenses. First we shall examine opsonisation potential in neutrophils by genotyping the Fc-gamma genes. Second, we shall consider the genetic bias towards Th1 or Th2 responses in these patients and finally we shall use microarray analysis to define novel and hitherto unsuspected targets for future genetic and therapeutic studies. By integrating molecular immunogenetic techniques into a cross-sectional and longitudinal epidemiological study, it is our goal to ultimately develop a genetic susceptibility profile which can be used to identify children who are at risk from LAP. Additionally, the data harvested from these studies should allow earlier treatment of disease and enhance our understanding of the molecular mechanisms underlying the pathogenesis of LAP and other forms of periodontitis.

描述（由申请人提供）：局部侵袭性牙周炎（LAP）是一种严重的疾病，通常会给受害者留下明显的、不可逆转的身体疤痕。非裔美国儿童患这种疾病的可能性比白人儿童高出十五倍，但这种不平衡的原因完全未知。家庭聚集和这种种族差异表明易感性有很强的遗传因素，但其分子基础目前尚不清楚。这种缺乏了解阻碍了预防措施和早期治疗的发展。已知这种疾病与伴放线放线杆菌有主要关联。最近的证据，包括我们的初步数据，表明用于对细菌做出反应的免疫系统基因的遗传变异在 LAP 的遗传易感性中发挥着重要作用。本研究的主要目的是确定影响非裔美国人 LAP 发生的基因。我们建议检查三个独立但相关的基因组，每个基因组都涵盖了人类抗菌防御的互补方面。首先，我们将通过对 Fc-gamma 基因进行基因分型来检查中性粒细胞的调理潜力。其次，我们将考虑这些患者对 Th1 或 Th2 反应的遗传偏向，最后我们将使用微阵列分析来为未来的遗传和治疗研究定义新颖且迄今为止未被怀疑的目标。通过将分子免疫遗传学技术整合到横断面和纵向流行病学研究中，我们的目标是最终开发出遗传易感性谱，可用于识别有 LAP 风险的儿童。此外，从这些研究中获得的数据应该能够更早地治疗疾病，并增强我们对 LAP 和其他形式牙周炎发病机制的分子机制的理解。