Subclinical CVD in African American Type 2 Diabetics

描述（由申请人提供）：非洲裔美国人糖尿病心脏研究的长期目标是确定非洲裔美国人（AA） 2型糖尿病（T2DM）受试者中动脉粥样硬化斑块钙化量明显低于欧洲裔美国人（EA）的原因。其他目标是评估生活方式、环境和遗传因素对亚临床心血管疾病（CVD）发展的影响，并确定与AAs合并T2DM的亚临床心血管疾病遗传成分相关的基因组区域。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，以先前在母体糖尿病心脏研究（DHS）中进行的工作为基础来实现。具体来说，我们将从另外566名不相关的AA合并T2DM患者中确定、表型和收集DMA，并将他们的信息与之前招募到DHS的90名不相关的AA糖尿病患者（共656名受试者）相结合。将为每位参与者创建临床风险因素档案，我们将使用冠状动脉、颈动脉和肾下主动脉的多排计算机断层扫描评估亚临床和临床CVD。接下来，我们将研究传统的心血管疾病危险因素（吸烟、血脂和脂蛋白、高血压和血糖控制）和新的危险因素（性激素和其他内分泌测量、钙调节激素、钙化抑制剂和炎症生物标志物）对AAs合并T2DM中钙化动脉粥样硬化斑块发展的影响。我们将通过将上述结果与来自美国国土安全局的2型糖尿病EA受试者的匹配队列结果进行比较，来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，我们将使用混合连锁不平衡图谱（MALD）筛选1100名无关联的AA型T2DM患者的基因组样本（444名先前在现有研究中招募，656名本地招募），以定位糖尿病AA人群中含有钙化动脉粥样硬化斑块易感基因的基因组区域。这些策略将为亚临床CVD的显著种族差异的原因提供新的信息，将有助于识别AA合并T2DM患者易患CVD的基因，并可能导致新的治疗策略的发展，以防止动脉硬化。

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.