Gene Mapping of Susceptibility to Periodontitis

牙周炎易感性基因定位

• 批准号: 7114837
• 负责人: SCOTT R DIEHL
• 金额: $ 36.06万
• 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: 2004
• 资助国家: 美国
• 起止时间: 2004-09-20 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114837
• 关键词: Actinobacillus actinomycetemcomitans; Bacteroides gingivalis; antibody titering; antigen antibody reaction; bioinformatics; chronic disease /disorder; clinical research; computational biology; disease /disorder classification; disease /disorder etiology; disease /disorder proneness /risk; family genetics; gene environment interaction; genetic mapping; genetic susceptibility; genotype; human genetic material tag; human subject; patient oriented research; periodontitis; single nucleotide polymorphism; smoking; twin /multiplet

DESCRIPTION: Substantial evidence indicates that genetic differences among individuals have a major effect on risk of chronic periodontitis. It is very likely this disease has a complex etiology, however, with inherited variation at multiple genes interacting with environmental factors such as smoking, hygiene, exposure to pathogens to determine individuals' disease risk. Our studies of adult twins demonstrated heritability of 50% and higher for quantitative measures such as mean attachment loss (AL) and percentage of sites with AL greater than thresholds of 2 mm, 3 mm or 4 mm. Our gene mapping analyses of early onset aggressive periodontitis families have identified dozens of candidate genes with strong to moderate support for involvement in this disease subtype. We have also recently shown that periodontitis-related phenotypes such as serum immunoglobulin levels have highly significant heritability. Major advances in human molecular genomics techniques for analysis of single nucleotide polymorphisms (SNPs) and statistical genetic strategies such as haplotype mapping may provide greatly increased power to identify genes underlying complex traits such as periodontitis. A critical component needed for success in this approach is availability of very large, high quality clinical populations. We propose to apply these tools and approaches to advance understanding of the genetic and environmental basis of susceptibility to chronic periodontitis by testing over 500 SNPs in over 100 candidate genes for association with periodontitis in i.) 7,300 subjects from the NHANES III study for whom DNA is available; ii.) 200 adult subjects with severe chronic periodontitis and 100 healthy controls recruited in Minnesota; and iii.) in 234 subjects from our previously reported twin study that demonstrated high heritability of chronic periodontitis; iv) by evaluating alternative quantitative and disease classification (discrete) measures in these clinical populations; and v.) by analyzing environmental risk factors in all samples and antibody responses to periodontal pathogens in the NHANES sample.

描述：大量证据表明个体之间的遗传差异对慢性牙周炎的风险有重大影响。然而，这种疾病很可能具有复杂的病因，多个基因的遗传变异与吸烟、卫生、接触病原体等环境因素相互作用，从而确定个体的疾病风险。我们对成年双胞胎的研究表明，定量测量的遗传力为 50% 或更高，例如平均依恋丧失 (AL) 和 AL 大于 2 毫米、3 毫米或 4 毫米阈值的部位百分比。我们对早发侵袭性牙周炎家族的基因图谱分析已经确定了数十个候选基因，这些基因对参与这种疾病亚型具有强到中度的支持。我们最近还表明，牙周炎相关表型（例如血清免疫球蛋白水平）具有高度显着的遗传性。用于分析单核苷酸多态性（SNP）的人类分子基因组学技术和统计遗传策略（例如单倍型作图）的重大进步可能会大大增强识别牙周炎等复杂性状背后的基因的能力。这种方法成功所需的一个关键因素是拥有大量、高质量的临床人群。我们建议应用这些工具和方法来加深对慢性牙周炎易感性的遗传和环境基础的理解，方法是测试 100 多个与牙周炎相关的候选基因中的 500 多个 SNP。 i.) 来自 NHANES III 研究的 7,300 名可获得 DNA 的受试者； ii.) 在明尼苏达州招募了 200 名患有严重慢性牙周炎的成年受试者和 100 名健康对照者； iii.) 在我们之前报道的双胞胎研究中的 234 名受试者中，证明了慢性牙周炎的高遗传性； iv) 通过评估这些临床人群中的替代定量和疾病分类（离散）措施； v.) 通过分析所有样本中的环境风险因素以及 NHANES 样本中牙周病原体的抗体反应。