Genetic Regulation of Adiposity and Associated CVD Risks

肥胖和相关心血管疾病风险的基因调控

• 批准号: 6802707
• 负责人: BRADFORD TOWNE
• 金额: $ 54.31万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-20 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6802707
• 关键词: adipose tissue; age difference; cardiovascular disorder risk; clinical research; gender difference; gene expression; genetic markers; genetic regulation; genotype; glucose metabolism; human subject; linkage mapping; lipid metabolism; longitudinal human study; magnetic resonance imaging; obesity; photon absorptiometry; polymerase chain reaction; quantitative trait loci; racial /ethnic difference

DESCRIPTION (provided by applicant): The main goal of the proposed study is to discover genes that jointly influence measures of adiposity and associated cardiovascular disease (CVD) risks, with the ultimate objective being to elucidate the role of new adiposity genes as mediators of related CVD risks. Specifically, we propose to focus on measures of abdominal visceral fat and abdominal subcutaneous fat obtained from magnetic resonance imaging (MRI), and measures of total body fat and regional body fat obtained from dual energy x-ray absorptiometry (DXA), and determine the nature of their genetic associations with particular sets of CVD risks known to be influenced by adiposity. These CVD risks include measures of recently discovered adipocyte-derived hormones, lipid and lipoprotein concentrations, glucose metabolism, and markers of vascular inflammation. These data will be collected from 1,013 individuals in large multi-generation families who range in age from 8 to 94 years, are represented equally by men and women, and include both Whites and African Americans. The proposed study leverages existing resources made available by the established Fels Longitudinal Study and the newer Miami Valley Family Aging Study. The study will use new technologies to quantify the amount, type, and distribution of adipose tissue in the body; examine age, sex, and ethnic differences in the relationships between measures of adiposity and related CVD risks; assess the role of adipose tissue as a metabolically active endocrine organ; quantify newly discovered adipocyte-derived hormones; assess the relationships between adiposity and vascular inflammation; and assess the relationships between adiposity and lipid and lipoprotein metabolism. The proposed study consists of four specific aims: 1) collect familial adiposity and associated CVD risk data using innovative technologies, 2) examine sex, age, and ethnicity differences in adiposity and associated CVD risks at the phenotypic level, 3) determine the general nature of shared genetic influences on adiposity and associated CVD risks using quantitative genetic analysis methods, and 4) identify quantitative trait loci (QTL) containing specific genes that jointly influence adiposity and associated CVD risks using variance components-based linkage analysis methods. Investigators on the proposed study have expertise in body composition analysis, cardiovascular disease, statistical genetic methodology, molecular genetics, growth and development, and aging.

描述(申请人提供)：拟议研究的主要目标是发现共同影响肥胖测量和相关心血管疾病(CVD)风险的基因，最终目的是阐明新的肥胖基因作为相关CVD风险的媒介所起的作用。具体地说，我们建议重点关注通过磁共振成像(MRI)获得的腹部内脏脂肪和腹部皮下脂肪的测量，以及通过双能X射线吸收法(DXA)获得的全身脂肪和局部体脂的测量，并确定它们与已知受肥胖症影响的特定组心血管疾病风险的遗传关联的性质。这些心血管风险包括最近发现的脂肪细胞衍生激素、脂和脂蛋白浓度、葡萄糖代谢和血管炎症标志物的测量。这些数据将从1013个多代大家庭的个人中收集，这些家庭的年龄从8岁到94岁不等，由男性和女性平等代表，包括白人和非裔美国人。拟议的研究利用了已建立的FELS纵向研究和较新的迈阿密山谷家庭老龄化研究提供的现有资源。这项研究将使用新技术来量化体内脂肪组织的数量、类型和分布；检查年龄、性别和种族差异，以衡量肥胖指标与相关心血管疾病风险之间的关系；评估脂肪组织作为代谢活跃的内分泌器官的作用；量化新发现的脂肪细胞衍生激素；评估脂肪与血管炎症之间的关系；以及评估脂肪与脂肪和脂蛋白代谢之间的关系。这项研究包括四个具体目标：1)使用创新技术收集家族性肥胖和相关的心血管疾病风险数据；2)在表型水平上检查肥胖和相关心血管风险的性别、年龄和种族差异；3)使用定量遗传分析方法确定共同基因对肥胖和相关心血管风险影响的一般性质；以及4)使用基于方差分量的连锁分析方法确定包含共同影响肥胖和相关心血管风险的特定基因的数量性状基因座(QTL)。这项拟议研究的研究人员在身体成分分析、心血管疾病、统计遗传学方法学、分子遗传学、生长发育和衰老方面拥有专业知识。