Gene Mapping of Susceptibility to Periodontitis

牙周炎易感性基因定位

• 批准号: 6949938
• 负责人: SCOTT R DIEHL
• 金额: $ 36.93万
• 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/6949938
• 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。但是，这种疾病很可能具有复杂的病因，但是，多个基因的遗传变异与吸烟，卫生，暴露于病原体等环境因素相互作用，以确定个体的疾病风险。我们对成年双胞胎的研究表明，定量措施（例如平均依恋损失（AL））和Al阈值大于2 mm，3 mm或4 mm的地点的遗传力为50％和更高。我们对早期发作侵袭性牙周炎家族的基因映射分析已经确定了数十个候选基因，具有强烈至中度支持，以参与这种疾病亚型。我们最近还表明，与牙周炎相关的表型（如血清免疫球蛋白水平）具有非常明显的遗传力。人分子基因组学技术的重大进展，用于分析单核苷酸多态性（SNP）和统计遗传策略（例如单倍型映射）可能会大大提高能力来识别诸如牙周炎等复杂性状的基因。在这种方法中，成功所需的关键组成部分是可用的非常大，高质量的临床人群。我们建议采用这些工具和方法，以通过测试超过100个候选基因中的500多个SNP来提高对慢性牙周炎易感性的遗传和环境基础的理解。 ii。）200名患有严重慢性牙周炎和100个健康对照的成年受试者在明尼苏达州招募； iii。）在我们先前报道的双胞胎研究中，有234名受试者表明慢性牙周炎的遗传力很高； 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；和v。）通过分析所有样品中的环境风险因素以及对NHANES样品中牙周病原体的抗体反应。