Subclinical CVD in African American Type 2 Diabetics

描述（由申请方提供）：非裔美国人-糖尿病心脏研究的长期目的是确定非裔美国人（AA）2型糖尿病（T2 DM）受试者钙化动脉粥样硬化斑块量显著低于欧洲裔美国人（EA）的原因。其他目标是评价生活方式、环境和遗传因素对亚临床心血管疾病（CVD）发生的影响，并确定导致T2 DM AA患者亚临床CVD遗传成分的基因组区域。这些目标将通过临床医生，流行病学家，生物统计学家，生物化学家和分子遗传学家的共同努力来实现，并建立在先前在母体糖尿病心脏研究（DHS）中进行的工作基础上。具体而言，我们将从另外566例不相关的T2 DM AA中确定、表型并收集DMA，将其信息与之前招募到DHS中的90例不相关的AA糖尿病受试者（共656例受试者）相结合。将为每名受试者创建临床风险因素特征，我们将使用冠状动脉和颈动脉以及肾下主动脉的多探测器行计算机断层扫描评估亚临床和临床CVD。我们接下来将研究传统CVD风险因素（吸烟、脂质和脂蛋白、高血压和血糖控制）和新风险因素（性激素和其他内分泌指标、钙调节激素、钙化抑制剂和炎症生物标志物）对T2 DM AA患者钙化动脉粥样硬化斑块发展的影响。我们将通过比较上述结果与来自母DHS的EA T2 DM受试者的匹配队列中获得的结果，研究钙化动脉粥样硬化斑块的种族差异。在第4年和第5年，我们将使用混合物连锁不平衡作图（MALD）在1，100例T2 DM无关AA受试者（444例先前在现有研究中招募，656例当地招募）的扩大样本中筛选基因组，以定位糖尿病AA人群中携带钙化动脉粥样硬化斑块易感基因的基因组区域。这些策略将提供关于亚临床CVD中显著种族差异原因的新信息，将有助于识别T2 DM AA受试者中易患CVD的基因，并可能导致开发新的治疗策略以预防动脉硬化。

DESCRIPTION (provided by applicant): The long term objective of the African American-Diabetes Heart Study is to identify the causes of the markedly lower amounts of calcified atherosclerotic plaque in African American (AA) subjects with type 2 diabetes mellitus (T2DM), relative to European Americans (EA). Additional goals are to evaluate the impacts of lifestyle, environment and inherited factors on the development of subclinical cardiovascular disease (CVD), and to identify genomic regions contributing to the inherited component of subclinical CVD in AAs with T2DM. These goals will be achieved by the concerted efforts of clinicians, epidemiologists, biostatisticians, biochemists, and molecular geneticists, building on work that was previously performed in the parent Diabetes Heart Study (DHS). Specifically, we will ascertain, phenotype, and collect DMA from an additional 566 unrelated AAs with T2DM, combining their information with 90 unrelated AA diabetic subjects previously recruited into the DHS (656 subjects total). Clinical risk factor profiles will be created for each participant and we will assess subclinical and clinical CVD using Multi-Detector Row Computed Tomography of the coronary and carotid arteries and infra-renal aorta. We will next examine the impact of conventional CVD risk factors (smoking, lipids and lipoproteins, hypertension and glycemic control) and novel risk factors (sex hormones and other endocrine measures, calcium regulating hormones, calcification inhibitors and inflammatory biomarkers) on the development of calcified atherosclerotic plaque in AAs with T2DM. We will investigate ethnic differences in calcified atheromatous plaque by comparing the above results with those obtained in a matched cohort of EA subjects with T2DM from the parent DHS. In years 4 and 5, we will screen the genome using Mapping by Admixture Linkage Disequilibrium (MALD) in an expanded sample of 1,100 unrelated AA subjects with T2DM (444 previously recruited in existing studies and 656 locally recruited) to locate genomic regions that harbor calcified atherosclerotic plaque susceptibility genes in the diabetic AA population. These strategies will provide novel information on causes of the marked ethnic disparity in subclinical CVD, will assist in identifying genes that predispose to CVD in AA subjects with T2DM, and may lead to the development of novel treatment strategies to prevent hardening of the arteries.