EPIDEMIOLOGY/GENE MAPPING OF EARLY ONSET PERIODONTITIS

早发性牙周炎的流行病学/基因图谱

• 批准号: 6954491
• 负责人: SCOTT R DIEHL
• 金额: $ 45.85万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 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 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6954491
• 关键词: clinical research; cooperative study; diet; disease /disorder onset; enzyme activity; family genetics; gene environment interaction; gene expression; gene mutation; genetic disorder; genetic polymorphism; genetic screening; genetic susceptibility; human subject; immunoglobulins; interleukin 1; linkage mapping; periodontitis; phenotype; platelet activating factor; polymerase chain reaction; quantitative trait loci; smoking; statistics /biometry; toothbrushing

Project 2: Genetic Epidemiology and Molecular Gene Mapping Studies of Early Onset Periodontitis Substantial evidence indicates that genetic differences among individuals influence risk of early onset periodontitis (EOP). However, this disease clearly has a complex etiology. Both heritable variation and factors in the environment (e.g., smoking, hygiene, exposure to pathogens) appear to interact in determining disease risk. Our previous studies demonstrated an association or interleukin-1 polymorphisms and EOP susceptibility. Other possible susceptibility genes were mapped to chromosomal regions but not yet specifically identified. We also initiated gene mapping studies of EOP-related phenotypes such as smoking behavior and serum immunoglobulins. Recent major advances in human molecular genomics and statistical genetic epidemiology provide greatly increased power in human molecular genomics and statistical genetic epidemiology provide greatly increased power to identify genes underlying complex traits such as EOP. We propose to apply these tools and approaches to follow up our previous findings for EOP by: i) verifying the role of IL-1 in EOP through analyses of additional IL-1 polymorphisms and additional EOP families and case-control subjects; ii) replicating our other gene mapping EOP findings using additional EOP families, identifying disease genes via mutational screening, evaluating new candidate gene polymorphisms and, when assay technologies mature, performing genome-wide disequilibrium mapping; iii) analyzing risk factor phenotypes such as smoking and immunoglobulin levels, both as covariates for EOP analyses and as highly heritable traits of direct interest; and iv) developing and evaluating quantitative measurements of EOP in lieu of the current discrete disease state classification and using these quantitative traits for re-analyses of our gen mapping data with variance components analyses and other quantitative trait locus (QTL) methods.

项目2：早发性牙周炎的遗传流行病学和分子基因图谱研究大量证据表明个体之间的遗传差异影响早发性牙周炎（EOP）的风险。然而，这种疾病显然具有复杂的病因。遗传变异和环境因素（例如吸烟、卫生、接触病原体）似乎在确定疾病风险方面相互作用。我们之前的研究证明了 IL-1 多态性与 EOP 易感性之间的关联。其他可能的易感基因已被定位到染色体区域，但尚未具体鉴定。我们还启动了 EOP 相关表型（例如吸烟行为和血清免疫球蛋白）的基因图谱研究。人类分子基因组学和统计遗传流行病学的最新重大进展大大增强了人类分子基因组学和统计遗传流行病学的能力，大大增强了识别 EOP 等复杂性状背后的基因的能力。我们建议应用这些工具和方法来跟进我们之前对 EOP 的发现： i) 通过分析其他 IL-1 多态性和其他 EOP 家族以及病例对照受试者来验证 IL-1 在 EOP 中的作用； ii) 使用其他 EOP 家族复制我们的其他基因作图 EOP 结果，通过突变筛选鉴定疾病基因，评估新的候选基因多态性，并在分析技术成熟时进行全基因组不平衡作图； iii) 分析危险因素表型，例如吸烟和免疫球蛋白水平，既作为 EOP 分析的协变量，又作为直接感兴趣的高度遗传性状； iv) 开发和评估 EOP 的定量测量，以代替当前离散的疾病状态分类，并使用这些数量性状通过方差分量分析和其他数量性状基因座 (QTL) 方法重新分析我们的基因作图数据。