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）：非裔美国人糖尿病心脏研究的长期目标是确定与欧洲裔美国人（EA）相对于欧洲人（EA）的2型糖尿病（T2DM）的非裔美国人（AA）受试者的钙化动脉粥样硬化斑块显着较低的原因。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，并确定促成T2DM AAS亚临床CVD遗传成分的基因组区域。这些目标将由临床医生，流行病学家，生物化学家，生物化学家和分子遗传学家的一致努力实现，这是基于以前在父母糖尿病心脏研究（DHS）中进行的工作的基础。具体而言，我们将确定，表型和收集与T2DM相关的566个无关的AAS，将其信息与以前招募到DHS的90名无关的AA糖尿病受试者相结合（总共656名受试者）。将为每个参与者创建临床风险因素谱，我们将使用冠状动脉和颈动脉和炎症性肾上腺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，我们将研究常规CVD危险因素（吸烟，脂质和脂蛋白，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，调节钙调节激素，钙化抑制剂和炎症生物标志物）对与钙化型动脉粥样硬化型与ASAS的钙化型胶质形成的发展。我们将通过将上述结果与来自父级DHS的T2DM的匹配的EA受试者进行比较，研究钙化的动脉瘤斑块中的种族差异。在4年级和5年级中，我们将使用混合链接不平衡（MALD）的映射在1,100个无关的AA受试者的样本中筛选基因组，该样本具有T2DM（444个先前在现有研究中招募的444个受试者和656个本地招聘的656个），以定位于糖尿病性的Plaque Plaque Plaque Suptibility Genes cance aaa aaa aaa aaa aaa aaa calcy calciple calliste calliste calliste callistate callistate callist calliste callist callist callist callist callos。这些策略将提供有关亚临床CVD中明显种族差异的原因的新颖信息，将有助于识别具有T2DM的AA受试者CVD的基因，并可能导致制定新的治疗策略以防止动脉硬化。