Genetics of Coronary Artery Disease in Alaska Natives

阿拉斯加原住民冠状动脉疾病的遗传学

• 批准号: 7006741
• 负责人: SVEN O EBBESSON
• 金额: $ 34.71万
• 依托单位: NORTON SOUND HEALTH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-27 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7006741
• 关键词: Alaskan Native American; Chlamydiaceae; atherosclerosis; atherosclerotic plaque; cardiovascular disorder epidemiology; carotid artery; clinical research; cooperative study; coronary artery; coronary disorder; electrocardiography; family genetics; gender difference; gene mutation; genetic markers; genetic polymorphism; genetic susceptibility; genotype; human population genetics; human subject; hypertension; interview; linkage mapping; obesity; phenotype; quantitative trait loci; ventricular hypertrophy

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is increasing among Alaska Natives. The Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study has been examining CVD and its risk factors by conducting a family genetic study among Eskimos residing in eight villages and the town of Nome in the Norton Sound Region. This application proposes to extend the GOCADAN study to pursue the following aims: 1) Expand the genetic studies that will emphasize the genome scan approach. The completed genome scan of 1214 members who are nearly all part of one extended pedigree will be used to identify quantitative trait loci for subclinical CVD and CVD risk factors and narrow the regions of interest by fine mapping. 2) Re-examine the family members so that changes in risk factors can be analyzed and genetic effects on changes estimated. Surveillance for CVD events will be instituted, including annual mortality surveillance and follow-up of nonfatal events uncovered at the time of the re-exam. Advantages of GOCADAN include: 1) It provides health data on an underserved ethnic group. 2) The large extended pedigree improves the chances of detecting significant loci for subclinical CVD and its risk factors. 3) Data from carotid ultrasound measures will improve understanding of mechanisms of vascular disease and the genetics of CVD. 4) A unique constellation of risk factors with low rates of several risk factors, such as diabetes and hypertension, but high levels of inflammation and rates of smoking, provides a population uniquely suited to examine the roles of inflammatory markers in CVD. GOCADAN will lead to valuable therapeutic and prevention strategies for this and other populations in the United States and the world, where the epidemics of obesity, diabetes, and CVD are increasing rapidly.

描述（由申请人提供）： 阿拉斯加原住民的心血管疾病（CVD）正在增加。阿拉斯加土著人（Gocadan）研究中冠状动脉疾病的遗传学一直在研究CVD及其危险因素，通过在居住在八个村庄和诺顿声音地区的诺姆镇的爱斯基摩人之间进行家庭遗传研究。该应用建议将Gocadan研究扩展到追求以下目的：1）扩大将强调基因组扫描方法的遗传研究。完成的1214名成员的完整基因组扫描将使用一个扩展的血统中的一部分，用于识别亚临床CVD和CVD危险因素的定量性状基因座，并通过精细映射范围缩小兴趣区域的范围。 2）重新检查家庭成员，以便可以分析风险因素的变化，并对估计变化的遗传影响。将对CVD事件进行监视，包括年度死亡率监视和重新审查时发现的非致命事件的随访。 Gocadan的优势包括：1）它在服务不足的种族上提供健康数据。 2）较大的扩展血统可以提高检测亚临床CVD及其危险因素的明显基因座的机会。 3）颈动脉超声措施的数据将提高人们对血管疾病机制和CVD遗传学的理解。 4）一个独特的危险因素星座，其率低的几个危险因素（例如糖尿病和高血压），但炎症和吸烟率的高水平为人们提供了一种非常适合检查CVD炎症标志物的作用的人群。 Gocadan将为美国和世界的其他人群提供宝贵的治疗和预防策略，这些人群的肥胖症，糖尿病和CVD的流行病正在迅速增加。