Telomere Attrition Rate and Periodontitis: a nested case control study in the ARI

端粒磨损率和牙周炎：ARI 中的一项巢式病例对照研究

• 批准号: 8277604
• 负责人: Anne E. Sanders
• 金额: $ 14.8万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-15 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277604
• 关键词: Academy; Adult; African American; Age; American; Atherosclerosis; Bacterial Infections; Biological; Biological Aging; Biological Markers; Blood; Blood specimen; Body mass index; Caucasoid Race; Centers for Disease Control and Prevention (U.S.); Characteristics; Chronic; Chronic Disease; Classification; Cohort Studies; Communities; County; DNA; Data; Dental; Diabetes Mellitus; Diet; Disadvantaged; Disease; Disease Progression; Environmental Risk Factor; Epidemiology; Fatty Acids; Frequencies; Genomics; Incidence; Incidence Study; Inflammation; Intervention Studies; Interview; Lead; Learning; Length; Leukocytes; Longitudinal Studies; Maryland; Measures; Mediating; Medical; Methods; Minnesota; Mississippi; Modality; Nested Case-Control Study; North Carolina; Omega-3 Fatty Acids; Oral cavity; Outcome; Oxidative Stress; Participant; Periodontal Attachment Loss; Periodontal Diseases; Periodontitis; Physical activity; Polymerase Chain Reaction; Population; Population Group; Prevalence; Process; Prospective Studies; Race; Recruitment Activity; Relative (related person); Research; Risk; Role; Sampling; Smoking; Social Environment; Societies; Socioeconomic Status; Subgroup; Testing; Time; Tissues; Variant; Visit; Washington; age related; aged; base; burden of illness; case control; cohort; design; disorder prevention; early onset; follow-up; high risk; insight; novel; novel strategies; prospective; sex; social disparities; socioeconomics; suburb; telomere; Academy; Adult; African American; Age; American; Atherosclerosis; Bacterial Infections; Biological; Biological Aging; Biological Markers; Blood; Blood specimen; Body mass index; Caucasoid Race; Centers for Disease Control and Prevention (U.S.); Characteristics; Chronic; Chronic Disease; Classification; Cohort Studies; Communities; County; DNA; Data; Dental; Diabetes Mellitus; Diet; Disadvantaged; Disease; Disease Progression; Environmental Risk Factor; Epidemiology; Fatty Acids; Frequencies; Genomics; Incidence; Incidence Study; Inflammation; Intervention Studies; Interview; Lead; Learning; Length; Leukocytes; Longitudinal Studies; Maryland; Measures; Mediating; Medical; Methods; Minnesota; Mississippi; Modality; Nested Case-Control Study; North Carolina; Omega-3 Fatty Acids; Oral cavity; Outcome; Oxidative Stress; Participant; Periodontal Attachment Loss; Periodontal Diseases; Periodontitis; Physical activity; Polymerase Chain Reaction; Population; Population Group; Prevalence; Process; Prospective Studies; Race; Recruitment Activity; Relative (related person); Research; Risk; Role; Sampling; Smoking; Social Environment; Societies; Socioeconomic Status; Subgroup; Testing; Time; Tissues; Variant; Visit; Washington; age related; aged; base; burden of illness; case control; cohort; design; disorder prevention; early onset; follow-up; high risk; insight; novel; novel strategies; prospective; sex; social disparities; socioeconomics; suburb; telomere

DESCRIPTION (provided by applicant): The biological mechanisms underlying racial and socioeconomic disparities in periodontitis are inadequately conceptualized, rarely investigated and poorly understood. Research by our group and others leads to the novel hypothesis that the earlier onset and greater burden of periodontitis in African American and low socioeconomic groups, relative to white race and more advantaged groups, is mediated by an accelerated rate of biological aging. We propose to test this hypothesis using a nested case control study within the prospective cohort Atherosclerosis Risk in Communities (ARIC) Study. This offers an efficient epidemiologic design that capitalizes on the respective strengths of both the case control and the prospective cohort designs. This study will undertake secondary analysis of existing data and stored biospecimen. Periodontitis cases will be compared with healthy controls in the community-based biracial ARIC Study. In 1987-1989, adults aged 45-64 years were recruited from four U.S. communities: Forsyth County, North Carolina; Jackson, Mississippi; suburban Minneapolis, Minnesota; and Washington County, Maryland. Interviews and examinations collected information on sociodemographic characteristics, medical status and biological samples including blood. At Visit 4, when the cohort was aged 54-73 years, 6,691 ARIC Study participants received a full mouth periodontal examination. Cases will be 160 adults with severe periodontitis defined according to a modified case classification of the Centers for Disease Control and Prevention and the American Academy of Periodontology. Controls, who do not have periodontitis (n=160), will be frequency-matched to cases (n=160) by sex, age in years and ARIC field center/race. The biomarker of biological age is leukocyte telomere length (LTL) measured in genomic DNA of stored blood samples collected at Visit 2 (1990-1992) and Visit 4 (1996-1998). DNA will be isolated using PureGene extraction. Relative LTL will be measured using a well- established method of quantitative polymerase chain reaction. Cross-sectional evidence shows that shorter LTL is associated with higher risk for many chronic and age-related disorders. To date, few prospective studies have measured rates of telomere attrition over time and even fewer of these have compared telomere attrition rates between cases and healthy controls. The study has three specific aims; each aim builds on the prior aim to develop a complete picture of the association of LTL and periodontitis, the rate of LTL attritio in cases and controls, and the degree to race and SES may modify this relationship. Explanatory variables are established risk and protective indicators for periodontitis including smoking, diabetes, body mass index, diet, physical activity, systemic inflammation and oxidative stress. Achieving all three of the aims will yield a complete and nuanced picture of the effect of biological aging, mediated by social context, on periodontitis outcomes. PUBLIC HEALTH RELEVANCE: This is a unique opportunity to learn about variation in rates of biological aging between population subgroups, and the role of biological age in the progression of periodontal destruction. Providing insights into the biological basis of social disparities in periodontitis will stimulate new approaches in modalities aimed at reducing the magnitude of disparities in periodontitis and the burden of this disease on society by targeting modifiable aspects of biological aging.

描述（由申请人提供）：牙周炎中种族和社会经济差异的生物学机制是不充分概念化的，很少研究且了解不足。我们小组和其他人的研究导致了一个新的假设，即非裔美国人和低社会经济群体的较早发作和更大的牙周炎负担相对于白人种族和更优势的群体，是由生物衰老的加速介导的。我们建议使用在社区（ARIC）研究中的前瞻性动脉粥样硬化风险中的嵌套案例对照研究来检验这一假设。这提供了有效的流行病学设计，该设计利用了案例控制和前瞻性队列设计的各自优势。这项研究将对现有数据进行次要分析，并存储生物测量。牙周炎病例将与基于社区的混血症研究中的健康对照组进行比较。 1987 - 1989年，从美国四个社区招募了45-64岁的成年人：北卡罗来纳州福赛斯县；密西西比州杰克逊；明尼苏达州明尼阿波利斯郊区；和马里兰州的华盛顿县。访谈和检查收集了有关社会人口统计学特征，医学状况和包括血液在内的生物样本的信息。在访问4时，当队列年龄在54-73岁之间时，有6,691名ARIC研究参与者接受了牙周检查。病例将是根据疾病控制与预防中心的改性病例分类和美国牙周病学研究中心的改性病例分类定义的160名成年人。没有牙周炎（n = 160）的对照组将按性别，年龄和ARIC野外中心/种族频率与病例（n = 160）进行频率（n = 160）。生物年龄的生物标志物是白细胞端粒长度（LTL），在访问2（1990-1992）收集的储存血液样本的基因组DNA中，并访问4（1996-1998）。 DNA将使用纯酸酯提取分离。相对LTL将使用良好的定量聚合酶链反应的方法进行测量。横截面证据表明，较短的LTL与许多慢性和年龄有关的疾病的风险较高。迄今为止，很少有前瞻性研究测量了随着时间的推移端粒损耗率，甚至更少的研究比较了病例和健康对照之间的端粒损耗率。该研究具有三个特定的目标。每个目标都建立在先前的目标基础上，以制定LTL和牙周炎关联，案例和控制中的LTL属性速率以及种族和SES的程度可能改变这种关系的全面情况。解释性变量是牙周炎的风险和保护指标，包括吸烟，糖尿病，体重指数，饮食，体育锻炼，全身炎症和氧化应激。实现这三个目标将产生由社会环境介导的生物衰老影响，对牙周炎结局介导的完整而细微的图景。 公共卫生相关性：这是了解人群亚组之间生物衰老率的差异以及生物年龄在牙周破坏进展中的作用的独特机会。提供对牙周炎社会差异的生物学基础的见解将刺激旨在减少牙周炎差异和这种疾病负担的方式，通过靶向可修改的生物衰老方面。