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

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尚未充分概念化，很少调查和了解。我们小组和其他人的研究导致了一个新的假设，即非洲裔美国人和低社会经济地位群体相对于白色种族和更多的白人群体，牙周炎的发病更早，负担更大，这是由生物老化的加速率介导的。我们建议在社区动脉粥样硬化风险（ARIC）前瞻性队列研究中使用嵌套病例对照研究来验证这一假设。这提供了一个有效的流行病学设计，利用病例对照和前瞻性队列设计各自的优势。本研究将对现有数据和储存的生物标本进行二次分析。牙周炎病例将在基于社区的birthiaric研究中与健康对照进行比较。在1987-1989年，从四个美国社区招募了45-64岁的成年人：北卡罗来纳州的福赛斯县;密西西比的杰克逊;明尼苏达州的明尼阿波利斯郊区;和马里兰州的华盛顿县。面谈和检查收集了关于社会人口特征、医疗状况和包括血液在内的生物样本的信息。在第4次访视时，当队列年龄在54-73岁时，6，691名ARIC研究参与者接受了全口牙周检查。病例将是160名患有严重牙周炎的成年人，根据疾病控制和预防中心和美国牙周病学会的修订病例分类进行定义。对照组，没有牙周炎（n=160），将按性别，年龄（岁）和ARIC现场中心/种族与病例（n=160）进行频率匹配。生物学年龄的生物标志物是在访视2（1990-1992）和访视4（1996-1998）时采集的储存血液样本的基因组DNA中测量的白细胞端粒长度（LTL）。将使用PureGene提取分离DNA。将使用成熟的定量聚合酶链反应方法测量相对LTL。横断面证据表明，较短的LTL与许多慢性和年龄相关疾病的风险较高相关。到目前为止，很少有前瞻性研究测量端粒随时间的磨损率，甚至更少的这些比较端粒磨损率之间的情况下和健康对照。该研究有三个具体目标;每个目标都建立在先前的目标之上，以全面了解LTL与牙周炎的相关性，病例和对照组的LTL磨损率，以及种族和SES的程度可能会改变这种关系。解释变量是牙周炎的既定风险和保护指标，包括吸烟、糖尿病、体重指数、饮食、体力活动、全身炎症和氧化应激。实现所有三个目标将产生一个完整的和微妙的图片的生物老化的影响，介导的社会背景下，牙周炎的结果。 公共卫生关系：这是一个独特的机会，了解人口亚组之间的生物老化率的变化，以及生物年龄在牙周破坏进展中的作用。深入了解牙周炎社会差异的生物学基础，将刺激新的方法，旨在减少牙周炎的差异程度和这种疾病对社会的负担，通过针对生物老化的可改变方面。