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: 7125426
• 负责人: Anthony G. Comuzzie
• 金额: $ 63.4万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 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/7125426
• 关键词: Alaskan Native American; Chlamydiaceae; atherosclerosis; atherosclerotic plaque; cardiovascular disorder epidemiology; carotid artery; clinical research; cooperative study; 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): GOCADAN (Genetics of Coronary Artery Disease in Alaska Natives) is a study of the relative contributions of genetic and environmental factors to cardiovascular disease (CVD) in Eskimos in the Norton Sound region of Alaska. CVD and its risk factors are increasing rapidly in Alaska Eskimos as their lifestyle and traditional diets become westernized. During Phase I, we have collected family data on 1214 GOCADAN participants. Initial analyses of the Phenotypic data show a high prevalence of atherosclerotic plaque and self-reported CVD, in the presence of favorable lipoprotein, blood pressure, and insulin resistance profiles, but high levels of smoking, pathogen burden, and C-reactive protein (CRP). Our genetic analyses show that key CVD risk factors have significant heritabilities, and have detected pleiotropic effects on CVD- related phenotypes. Our initial genome scan has identified promising quantitative trait loci (QTLs) for CVD-related phenotypes including a QTL for diabetes on chromosome 2q, a QTL for lipid levels on chromosome 19, and a QTL for blood pressure phenotypes on chromosome 2p. Because the data collected so far raise many unanswered questions concerning the relatives contribution of genes and environment to the high prevalence of atherosclerotic plaque and CVD in this population, we propose to continue this study with the following specific aims: 1) examine positional candidate genes in proximity to CVD risk factor QTLs using Bayesian quantitative trait nucleotide (QTN) analysis to identify genetic variation that accounts for our linkage signals, 2) continue genome-wide linkage and other quantitative genetic analyses of CVD-related phenotypes collected in Phase I and II examinations, including new phenotypes collected in Phase II, 3) assess the genetic contribution to changes in CVD-related phenotypes between Phase I (baseline) and Phase II (follow-up) examinations, and 4) continue to serve as the Data Coordinating Center and as a resource for Norton Sound Health Corporation, MedStar Research Institute and Cornell Medical Center in the Phase II re-examination of family members. This study should prove invaluable in the identification of genetic factor that interact with lifestyle and diet to increase susceptibility to CVD in both Alaskan Eskimos and the general population. GOCADAN will lead to valuable therapeutic and prevention strategies for Eskimos and other populations, where the epidemics of obesity, diabetes, and CVD are increasing rapidly.

描述（由申请人提供）： Gocadan（阿拉斯加土著人的冠状动脉疾病的遗传学）是对阿拉斯加诺顿声音区域中爱斯基摩人心血管疾病（CVD）的遗传和环境因素对心血管疾病（CVD）的相对贡献的研究。随着阿拉斯加爱斯基摩人的生活方式和传统饮食的西化，CVD及其危险因素正在迅速增加。在第一阶段，我们收集了有关1214名Gocadan参与者的家庭数据。对表型数据的初步分析表明，在存在有利的脂蛋白，血压和胰岛素抵抗谱的情况下，动脉粥样硬化斑块和自我报告的CVD的患病率很高，但吸烟，病原体负担和C反应蛋白（CRP）的含量很高。我们的遗传分析表明，关键的CVD风险因素具有明显的遗传性，并检测到对CVD相关表型的多效性影响。我们的最初基因组扫描已确定了与CVD相关的表型的有希望的定量性状基因座（QTL），包括染色体2q上的糖尿病的QTL，染色体19染色体上的脂质水平的QTL，以及染色体上血压表型的QTL QTL。 Because the data collected so far raise many unanswered questions concerning the relatives contribution of genes and environment to the high prevalence of atherosclerotic plaque and CVD in this population, we propose to continue this study with the following specific aims: 1) examine positional candidate genes in proximity to CVD risk factor QTLs using Bayesian quantitative trait nucleotide (QTN) analysis to identify genetic variation that accounts for our联系信号，2）继续在I和II阶段检查中收集的CVD相关表型的全基因组联系和其他定量遗传分析，包括在II期中收集的新表型，3）评估CVD相关表型的遗传贡献，用于CVD相关的表型的变化，用于II（基线）和II期（随访）和4），以及ATA和4）的研究，以及4）AT的研究，以及4），以及4）ATA和4），以及4），以及4）AN和4）以及4）以及4阶段的研究。诺顿桑德健康公司，MEDSTAR研究所和康奈尔医学中心的第二阶段重新检查家庭成员。这项研究应证明在与生活方式和饮食相互作用的遗传因素的鉴定中应该是无价的，以提高阿拉斯加爱斯基摩人和一般人群中对CVD的敏感性。 Gocadan将为Eskimos和其他人群提供宝贵的治疗和预防策略，在这种情况下，肥胖，糖尿病和CVD的流行病正在迅速增加。