IDENTIFYING GENES FOR OBESITY QTLS RELATED TO CVD

识别与 CVD 相关的肥胖 QTLS 基因

• 批准号: 8172661
• 负责人: Anthony G. Comuzzie
• 金额: $ 13.01万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172661
• 关键词: Adipose tissue; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Characteristics; Cholesterol; Chronic; Computer Retrieval of Information on Scientific Projects Database; Data; Diabetes Mellitus; Dietary Fats; Endocrine; Endocrine Glands; Fatty acid glycerol esters; Funding; Genes; Genetic; Grant; Human; Individual; Institution; Lipids; Mediating; Metabolic Pathway; Metabolism; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Papio; Phenotype; Physiological; Play; Proteins; Quantitative Trait Loci; Regulation; Research; Research Personnel; Resources; Risk; Role; Source; United States National Institutes of Health; blood glucose regulation; density; glucose metabolism; numb protein

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adipose tissue plays an important role in maintaining normal physiological functions associated with lipid and glucose metabolism such that the disruption of these functions leads to increasing risks for both cardiovascular disease and type 2 diabetes. The mechanisms by which adipose tissue mediates an individual's risk of developing cardiovascular disease and diabetes are not clearly understood. However, results of recent studies have demonstrated that adipose tissue is an active endocrine organ producing a number of proteins. These proteins have potent effects on a variety of metabolic pathways and in particular appear to exert a significant effect on lipid and glucose regulation. In addition, there is growing evidence that dietary make-up, particularly the fat and cholesterol content, can have significant effects on the expression of many genes involved in metabolic processes including those associated with adipose tissue function. As part of the current study, we have now begun to identify quantitative trait loci (QTLs) with significant effects on the regulation of adipose tissue function and to assess their impact on cardiovascular disease and type 2 diabetes. We propose to examine the effects of specific positional candidate genes for significant QTLs on phenotypes related to adiposity and adipose tissue endocrine function. We will evaluate further the relevance for humans of detected candidate gene associations in the baboon by conducting replication analyses using high density SNP data from a large-scale human cardiovascular genetics study. We also propose to examine the effects of a chronic high cholesterol, high fat dietary challenge on the composition and function of adipose tissue and to determine how changes in the characteristics of adipose tissue relate to changing risk profiles for cardiovascular disease and diabetes.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 脂肪组织在维持与脂质和葡萄糖代谢相关的正常生理功能中起重要作用，使得这些功能的破坏导致心血管疾病和2型糖尿病的风险增加。脂肪组织介导个体患心血管疾病和糖尿病风险的机制尚不清楚。然而，最近的研究结果表明，脂肪组织是一个活跃的内分泌器官，产生许多蛋白质。这些蛋白质对多种代谢途径具有有效作用，特别是似乎对脂质和葡萄糖调节产生显著影响。此外，越来越多的证据表明，饮食组成，特别是脂肪和胆固醇含量，可以对参与代谢过程的许多基因的表达产生显着影响，包括与脂肪组织功能相关的基因。作为当前研究的一部分，我们现在已经开始鉴定具有显著效应的数量性状位点（QTL 调节脂肪组织功能，并评估其对心血管疾病和2型糖尿病的影响。我们建议检查特定位置的候选基因的显着QTL的肥胖和脂肪组织内分泌功能相关的表型的影响。我们将进一步评估 通过使用来自大规模人类心血管遗传学研究的高密度SNP数据进行复制分析，确定狒狒中检测到的候选基因关联与人类的相关性。我们还建议检查慢性高胆固醇，高脂肪饮食挑战对脂肪组织的组成和功能的影响，并确定脂肪组织特征的变化如何与心血管疾病和糖尿病风险状况的变化相关。