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的生物学机制没有被充分概念化，很少被研究，也很少被理解。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相对于白人和更有优势的群体，牙周炎的发病更早和负担更重，是由生物老龄化的加速速度所调节的。我们建议使用前瞻性队列人群动脉粥样硬化风险(ARIC)研究中的嵌套病例对照研究来检验这一假设。这提供了一种有效的流行病学设计，它充分利用了病例对照设计和前瞻性队列设计的各自优势。这项研究将对现有数据和储存的生物制品进行二次分析。在以社区为基础的ARIC研究中，牙周炎病例将与健康对照进行比较。1987年至1989年，从四个美国社区招募了年龄在45-之间的成年人：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华盛顿县。访谈和检查收集了有关社会人口学特征、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，当队列的年龄为54-73岁时，6691名ARIC研究参与者接受了全口牙周检查。根据疾病控制和预防中心和美国牙周病学学会修改后的病例分类，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领域中心/种族与病例(n=160)进行频率匹配。生物学年龄的生物标记物是在访视2(1990-1992年)和访视4(1996-1998年)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)。DNA将使用纯基因提取法进行分离。将使用成熟的定量聚合酶链式反应方法来测量相对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有关。到目前为止，很少有前瞻性研究测量端粒随时间的磨损率，其中更少的研究比较了病例和健康对照组之间的端粒磨损率。这项研究有三个具体目标；每个目标都建立在先前目标的基础上，即全面了解LTL与牙周炎的关系，病例和对照中LTL的发生率，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。实现所有这三个目标将产生一个完整和细微差别的图景，由社会背景介导的生物老龄化对牙周炎结果的影响。 公共卫生相关性：这是一个独特的机会，可以了解不同人口亚组之间生物老龄化速度的差异，以及生物年龄在牙周破坏进展中的作用。提供对牙周炎社会差异的生物学基础的见解将刺激新的方法，旨在通过针对生物老化的可改变的方面来减少牙周炎的差异的程度和这种疾病对社会的负担。

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.