Subclinical CVD in African American Type 2 Diabetics

非裔美国人 2 型糖尿病患者的亚临床 CVD

• 批准号: 7636852
• 负责人: BARRY Ira FREEDMAN
• 金额: $ 64.57万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7636852
• 关键词: Admixture; Affect; African American; Alabama; Albuminuria; American; Aorta; Arterial Fatty Streak; Arteries; Atherosclerosis; Biochemical; Biochemical Genetics; Biological Markers; Blood Pressure; Blood Vessels; Calcified; Calcium; Cardiovascular Diseases; Carotid Arteries; Carotid Artery Ulcerating Plaque; Chromosome Mapping; Clinical; Cohort Studies; Collaborations; Complex; Coronary; Coronary artery; DNA; Data; Databases; Detection; Development; Diabetes Mellitus; Diet; Disease; Employee Strikes; Endocrine; Ensure; Environment; Environmental Risk Factor; Epidemiologist; Ethnic Origin; European; Exercise; Family; Family Study; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genome; Genomics; Genotype; Goals; Gonadal Steroid Hormones; Heart; Hormones; Hypertension; Image; Inflammation; Inflammatory; Inherited; Kidney; Laboratories; Lead; Letters; Life Style; Linkage Disequilibrium; Linkage Disequilibrium Mapping; Lipids; Lipoproteins; Maps; Measures; Medicine; Mentors; Modeling; Molecular; Molecular Genetics; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Parents; Participant; Pathway interactions; Phenotype; Plasma; Population; Public Health Schools; Questionnaires; Reading; Recruitment Activity; Relative (related person); Reporting; Research Infrastructure; Research Personnel; Residual state; Resources; Risk Factors; Role; Sampling; Scanning; Schools; Severities; Siblings; Smoking; Study Subject; Susceptibility Gene; Universities; Vascular calcification; Woman; Work; X-Ray Computed Tomography; base; bone; calcification; calcification inhibitor; calcium metabolism; cardiovascular disorder risk; cohort; cost; cost effective; detector; diabetic; ethnic difference; forest; genetic analysis; genetic epidemiology; genetic risk factor; glycemic control; inhibitor/antagonist; insight; men; mineralization; novel; prevent; programs; promoter; repository; treatment strategy

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.

描述(由申请人提供)：非裔美国人-糖尿病心脏研究的长期目标是确定非裔美国人(AA)2型糖尿病(T2 DM)患者钙化动脉粥样硬化斑块数量明显低于欧洲美国人(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，并确定在伴发T2 DM的AAS中导致亚临床心血管疾病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，在母公司糖尿病心脏研究(DHS)之前所做工作的基础上实现。具体地说，我们将从另外566名与T2 DM无关的AA中确定、表型和收集DMA，结合他们的信息和之前招募到DHS的90名无关AA糖尿病患者(总共656名受试者)。我们将为每个参与者创建临床风险因素档案，我们将使用冠状动脉、颈动脉和肾下动脉的多排计算机断层扫描来评估亚临床和临床心血管疾病。接下来，我们将考察传统的心血管危险因素(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措施、钙调节激素、钙化抑制剂和炎症生物标志物)对2型糖尿病合并AAS患者钙化动脉粥样硬化斑块形成的影响。我们将通过将上述结果与来自父母DHS的匹配的患有T2 DM的EA受试者的结果进行比较，来调查钙化动脉粥样斑块的种族差异。在第4年和第5年，我们将在1,100名与T2 DM无关的AA受试者(现有研究中招募的444人，本地招募的656人)的扩大样本中使用混合链接不平衡(MALD)筛选基因组，以定位糖尿病AA人群中包含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心血管疾病中显著的种族差异的原因提供新的信息，将有助于在患有T2 DM的再障患者中识别易患心血管疾病的基因，并可能导致开发新的治疗策略来防止动脉硬化。