IRAS FAMILY STUDY: GENETICS OF INSULIN RESISTANCE

IRAS 家庭研究：胰岛素抵抗的遗传学

• 批准号: 6527617
• 负责人: MOHAMMED F SAAD
• 金额: $ 9.35万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-15 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527617
• 关键词: African American; Hispanic Americans; adipose tissue; atherosclerosis; cardiovascular disorder; clinical research; computed axial tomography; disease /disorder proneness /risk; family genetics; gender difference; genetic mapping; genetic markers; genetic susceptibility; glucose tolerance test; human subject; insulin sensitivity /resistance; linkage mapping; phenotype; racial /ethnic difference

Insulin resistance is an important risk factor for atherosclerosis. Insulin sensitivity varies widely within populations and substantial evidence indicates that much of the variation can be attributed to genetic factors. Visceral adiposity, another important atherosclerosis risk factor, appears also to be genetically determined and correlates strongly with insulin resistance. The overall goals of this proposal are to: 1) identify the genetic determinants of insulin sensitivity and visceral adiposity; 2) determine the extent to which insulin sensitivity, visceral adiposity, and metabolic cardiovascular risk factors share common genetic influences. To address these goals, we will enroll family members of 160 African-American and Hispanic men and women who are currently participating in the Insulin Resistance Atherosclerosis Study (IRAS). Approximately 1280 family members will be recruited. Insulin sensitivity will be measured using the frequently sampled intravenous glucose tolerance test with minimal model analysis. Visceral adiposity will be assessed with computed tomography and traditional metabolic cardiovascular risk factors will be measured. 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 perform linkage disequilibrium analysis 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 genetic laboratory. Our center will examine 432 family members of 54 African-American participants in the IRAS. This project will contribute substantially to our understanding of the genetic determinants of insulin sensitivity, visceral adiposity, and the risk of atherosclerosis.

胰岛素抵抗是动脉粥样硬化的重要危险因素。 胰岛素敏感性在人群中差异很大，大量证据表明，大部分变异可归因于遗传因素。 内脏肥胖，另一个重要的动脉粥样硬化危险因素，似乎也是由遗传决定的，并与胰岛素抵抗密切相关。 该提案的总体目标是：1）确定胰岛素敏感性和内脏肥胖的遗传决定因素; 2）确定胰岛素敏感性、内脏肥胖和代谢性心血管危险因素共享共同遗传影响的程度。 为了实现这些目标，我们将招募160名目前正在参加胰岛素抵抗动脉粥样硬化研究（IRAS）的非洲裔美国人和西班牙裔男性和女性的家庭成员。 将招募约1280名家庭成员。 将使用频繁采样的静脉葡萄糖耐量试验和最小模型分析测量胰岛素敏感性。 内脏肥胖将通过计算机断层扫描进行评估，并测量传统的代谢性心血管危险因素。 将从DNA中对一组370个微卫星标记进行基因分型，并进行全基因组扫描，以检测含有影响表型变异的基因座的染色体区域。 然后，我们将用额外的标记使这些分析中鉴定的连锁区域饱和，并将进行连锁不平衡分析以进一步定位推定的基因座。 本研究的组织与IRAS相似，包括3个临床中心、1个协调中心、1个中心实验室和1个遗传实验室。 我们的中心将对54名非裔美国人参与IRAS的432名家庭成员进行检查。 这个项目将大大有助于我们了解胰岛素敏感性，内脏肥胖和动脉粥样硬化的风险的遗传决定因素。