IRAS FAMILY STUDY: GENETICS OF INSULIN RESISTANCE

IRAS 家庭研究：胰岛素抵抗的遗传学

• 批准号: 6527179
• 负责人: STEVEN M. HAFFNER
• 金额: $ 8.21万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527179
• 关键词: Hispanic Americans; atherosclerosis; body composition; cardiovascular disorder; clinical research; cooperative study; disease /disorder proneness /risk; family genetics; genetic mapping; genetic markers; genetic susceptibility; glucose tolerance test; human subject; insulin sensitivity /resistance; linkage disequilibriums; nucleic acid repetitive sequence; obesity; racial /ethnic difference

Insulin resistance is an important risk factor for atherosclerosis. Insulin resistance varies widely within populations, and substantial evidence indicates that much of this variation can be attributed to genetic sources. Visceral adiposity, another important atherosclerotic risk factor, is strongly correlated with insulin resistance, and this trait also appears to be under substantial genetic control. The overall goals of the proposed research project are to: 1) identify the genetic determinants of insulin resistance and visceral adiposity; and 2) determine the extent to which insulin resistance, visceral adiposity, and metabolic cardiovascular disease risk factors share common genetic influences. To address these goals, we will enroll 160 families of African-American and Hispanic background who are participating in the Insulin Resistance Atherosclerosis Study (IRAS). Approximately 1280 additional family members will be recruited. Insulin resistance will be measured using the frequently sampled intravenous glucose tolerance test, and visceral adiposity will be measured using computed tomography. A panel of other metabolic cardiovascular disease factors will also be assessed. A panel of 370 microsatellite markers will be genotyped from DNA, and a genome-wide scan will be performed to detect chromosomal regions containing loci that influence phenotypic variation. We will then saturate the regions of linkage identified in these analyses with additional markers and will then perform linkage disequilibrium analyses in effort to localize further the putative loci. The organization of this study will be similar to that of IRAS, with three clinical centers, a coordinating center, a central laboratory and a genetics laboratory. This center will be responsible for recruitment of Hispanics. This project will contribute substantially to our understanding of the genetic determinants of insulin sensitivity, and consequently to risk of atherosclerosis.

胰岛素抵抗是动脉粥样硬化的重要危险因素。 胰岛素抵抗在人群中差异很大，大量证据表明，这种变化的大部分可以归因于遗传来源。 内脏肥胖是另一个重要的动脉粥样硬化风险因素，与胰岛素抵抗密切相关，这种性状似乎也处于实质性遗传控制之下。 拟议的研究项目的总体目标是：1）确定胰岛素抵抗和内脏肥胖的遗传决定因素； 2）确定胰岛素抵抗，内脏肥胖和代谢心血管疾病危险因素具有共同遗传影响的程度。 为了解决这些目标，我们将招募160个参加胰岛素抵抗动脉粥样硬化研究（IRAS）的非裔美国人和西班牙裔背景。 将招募大约1280名其他家庭成员。 将使用经常采样的静脉葡萄糖耐量测试测量胰岛素抵抗，并使用计算机断层扫描来测量内脏肥胖。 还将评估其他代谢性心血管疾病因素。 将从DNA中对370个微卫星标记的面板进行基因分型，并将进行全基因组扫描以检测含有影响表型变异的基因座的染色体区域。 然后，我们将用其他标记饱和这些分析中确定的链接区域，然后进行连锁不平衡分析，以进一步定位推定的基因座。 这项研究的组织将与IRA的组织相似，其中三个临床中心，一个协调中心，一个中央实验室和一个遗传学实验室。 该中心将负责招募西班牙裔。 该项目将有助于我们对胰岛素敏感性的遗传决定因素的理解，从而有助于动脉粥样硬化的风险。