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

描述（由申请人提供）：牙周炎的种族和社会经济差异背后的生物学机制没有充分的概念化，很少调查和了解。我们的研究小组和其他人的研究提出了一个新的假设，即相对于白人和更有利的群体，非洲裔美国人和低社会经济群体的牙周炎发病更早，负担更重，是由生物衰老速度加快介导的。我们建议在前瞻性队列社区动脉粥样硬化风险（ARIC）研究中使用嵌套病例对照研究来验证这一假设。这提供了一种有效的流行病学设计，利用病例对照和前瞻性队列设计的各自优势。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双种族ARIC研究中与健康对照进行比较。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；密西西比州杰克逊的;明尼苏达州明尼阿波利斯郊区；以及马里兰州的华盛顿县。面谈和检查收集了有关社会人口特征、医疗状况和包括血液在内的生物样本的信息。在第4次访问中，当队列年龄为54-73岁时，6,691名ARIC研究参与者接受了全口牙周检查。根据疾病控制与预防中心和美国牙周病学会修订的病例分类，病例将是160名患有严重牙周炎的成年人。未患牙周炎的对照组（n=160）将按性别、年龄和ARIC场地中心/种族与病例（n=160）进行频率匹配。生物年龄的生物标志物是在访问2（1990-1992）和访问4（1996-1998）收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）。DNA将使用PureGene萃取法分离。相对LTL将使用一种完善的定量聚合酶链反应方法来测量。横断面证据显示，较短的LTL与许多慢性和年龄相关疾病的高风险相关。迄今为止，很少有前瞻性研究测量了端粒磨损率随时间的变化，甚至更少的研究比较了病例和健康对照之间的端粒磨损率。这项研究有三个具体目的；每个目标都建立在前一个目标的基础上，即全面了解牙周炎与牙周炎的关系，病例和对照组牙周炎的磨损率，以及种族和社会地位的程度可能会改变这种关系。解释变量是已确定的牙周炎风险和保护指标，包括吸烟、糖尿病、体重指数、饮食、身体活动、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细致入微的画面生物老化的影响，由社会背景介导，对牙周炎的结果。

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.