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：早期发作牙周炎的遗传流行病学和分子基因映射研究大量证据表明，个体之间的遗传差异会影响早期发作牙周炎（EOP）的风险。但是，这种疾病显然具有复杂的病因。可遗传的变异和环境中的因素（例如吸烟，卫生，暴露于病原体）似乎在确定疾病风险方面相互作用。我们以前的研究表明，缔合或白介素-1多态性和EOP敏感性。将其他可能的敏感性基因映射到染色体区域，但尚未明确鉴定。我们还启动了与EOP相关表型（例如吸烟行为和血清免疫球蛋白）的基因映射研究。人分子基因组学和统计遗传流行病学的最新主要进步在人分子基因组学方面提供了大大提高的功率，统计遗传流行病学为识别诸如EOP等复杂性状的基因提供了大大增加的能力。我们建议通过以下方式应用这些工具和方法来跟踪我们以前的EOP发现，通过以下方式通过分析额外的IL-1多态性以及其他EOP家族以及病例对照主题来验证IL-1在EOP中的作用； ii）使用其他EOP家族复制其他基因映射EOP发现，通过突变筛查鉴定疾病基因，评估新的候选基因多态性，以及分析技术成熟时，进行全基因组的不平衡映射； iii）分析危险因素表型，例如吸烟和免疫球蛋白水平，包括用于EOP分析的协变量和直接兴趣的高度遗传特征； iv）开发和评估EOP的定量测量，以代替当前的离散疾病状态分类，并使用这些定量性状对我们的GEN映射数据的重新分析，并使用方差组件分析和其他定量性状基因座（QTL）方法。