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。阿拉斯加原住民冠状动脉疾病遗传学 (GOCADAN) 研究一直在通过对居住在诺顿湾地区八个村庄和诺姆镇的爱斯基摩人进行家族遗传学研究来检查 CVD 及其危险因素。本申请建议扩展 GOCADAN 研究以实现以下目标： 1) 扩展强调基因组扫描方法的遗传研究。对几乎全部属于一个扩展谱系的 1214 名成员进行的完整基因组扫描将用于识别亚临床 CVD 和 CVD 风险因素的数量性状位点，并通过精细绘图缩小感兴趣区域。 2) 重新检查家庭成员，以便分析危险因素的变化并估计遗传对变化的影响。将建立对CVD事件的监测，包括年度死亡率监测以及对复查时发现的非致命事件进行随访。 GOCADAN 的优势包括： 1) 它提供服务不足的族群的健康数据。 2) 庞大的扩展谱系提高了检测亚临床CVD及其危险因素的重要位点的机会。 3) 颈动脉超声测量数据将增进对血管疾病机制和 CVD 遗传学的了解。 4) 一系列独特的危险因素，其中几种危险因素（如糖尿病和高血压）的发生率较低，但炎症水平和吸烟率较高，为研究炎症标志物在 CVD 中的作用提供了独特的人群。 GOCADAN 将为这一人群以及美国和世界各地的其他人群带来有价值的治疗和预防策略，这些地区的肥胖、糖尿病和心血管疾病的流行正在迅速增加。