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（阿拉斯加原住民冠状动脉疾病遗传学）是一项关于遗传和环境因素对阿拉斯加诺顿湾地区爱斯基摩人心血管疾病 (CVD) 的相对影响的研究。随着阿拉斯加爱斯基摩人的生活方式和传统饮食变得西化，CVD 及其危险因素正在迅速增加。在第一阶段，我们收集了 1214 名 GOCADAN 参与者的家庭数据。表型数据的初步分析显示，在存在有利的脂蛋白、血压和胰岛素抵抗特征，但吸烟、病原体负荷和 C 反应蛋白 (CRP) 水平较高的情况下，动脉粥样硬化斑块和自我报告的 CVD 患病率较高）。我们的遗传分析表明，关键的 CVD 危险因素具有显着的遗传性，并且已检测到对 CVD 相关表型的多效性影响。我们最初的基因组扫描已经确定了与 CVD 相关表型有前景的数量性状位点 (QTL)，包括 2q 染色体上的糖尿病 QTL、19 号染色体上的血脂水平 QTL 以及 2p 染色体上的血压表型 QTL。由于迄今为止收集的数据提出了许多未解答的问题，涉及基因和环境对该人群中动脉粥样硬化斑块和CVD高患病率的相关贡献，因此我们建议继续这项研究，其具体目标如下：1）检查位置候选基因使用贝叶斯数量性状核苷酸 (QTN) 分析来确定 CVD 风险因素 QTL 的接近程度，以识别解释我们的连锁信号的遗传变异，2) 继续对 CVD 相关表型进行全基因组连锁和其他定量遗传分析在第一阶段和第二阶段检查中收集的数据，包括在第二阶段收集的新表型，3) 评估第一阶段（基线）和第二阶段（后续）检查之间 CVD 相关表型变化的遗传贡献，以及 4) 继续作为诺顿桑德健康公司、MedStar 研究所和康奈尔医学中心在家庭成员第二阶段复查中的数据协调中心和资源。这项研究对于确定与生活方式和饮食相互作用的遗传因素具有不可估量的价值，这些因素会增加阿拉斯加爱斯基摩人和普通人群对心血管疾病的易感性。 GOCADAN 将为爱斯基摩人和其他人群带来有价值的治疗和预防策略，这些人群的肥胖、糖尿病和心血管疾病的流行正在迅速增加。