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

基本信息

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
项目类别：
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

项目摘要

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）：非洲裔美国人糖尿病心脏研究的长期目标是确定患有 2 型糖尿病 (T2DM) 的非洲裔美国人 (AA) 受试者中钙化动脉粥样硬化斑块数量明显减少的原因，相对而言，欧洲裔美国人 (EA)。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，并确定导致 2 型糖尿病 AA 中亚临床 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，并以先前在母公司糖尿病心脏研究 (DHS) 中进行的工作为基础。具体来说，我们将从另外 566 名不相关 AA 患有 T2DM 中确定、表型并收集 DMA，将其信息与之前招募到 DHS 的 90 名不相关 AA 糖尿病受试者（总共 656 名受试者）相结合。将为每位参与者创建临床危险因素概况，我们将使用冠状动脉、颈动脉和肾下主动脉的多探测器行计算机断层扫描来评估亚临床和临床 CVD。接下来，我们将研究传统 CVD 危险因素（吸烟、血脂和脂蛋白、高血压和血糖控制）和新型危险因素（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）对钙化形成的影响。 AA 合并 T2DM 中的动脉粥样硬化斑块。我们将通过将上述结果与来自父母 DHS 的 2 型糖尿病 EA 受试者匹配队列中获得的结果进行比较，研究钙化粥样斑块的种族差异。在第 4 年和第 5 年，我们将使用混合连锁不平衡作图 (MALD) 在 1,100 名不相关 AA 患有 T2DM 受试者（444 名先前在现有研究中招募的受试者和 656 名本地招募）的扩展样本中筛选基因组，以定位含有钙化的基因组区域糖尿病 AA 人群中的动脉粥样硬化斑块易感基因。这些策略将提供有关亚临床 CVD 中显着种族差异的原因的新信息，将有助于识别患有 T2DM 的 AA 受试者中易患 CVD 的基因，并可能导致开发新的治疗策略来预防动脉硬化。