HERITAGE-GENETICS, RESPONSE TO EXERCISE, RISK FACTORS-3

遗传遗传、运动反应、风险因素 3

• 批准号: 6526857
• 负责人: CLAUDE BOUCHARD
• 金额: $ 74.92万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6526857
• 关键词: African American; aerobic exercise; age difference; body composition; cardiovascular disorder epidemiology; cardiovascular stress test; caucasian American; clinical research; diabetes mellitus genetics; diabetes risk; family genetics; gene expression; gene mutation; genetic markers; genome; human data; human tissue; insulin; insulin sensitivity /resistance; linkage mapping; longitudinal human study; noninsulin dependent diabetes mellitus; pancreatic islet function; phenotype; racial /ethnic difference

The aim of the HERITAGE Family Study is to document the cardiovascular and metabolic responses to endurance training, and the contribution of genetic factors to the concomitant response of cardiovascular disease (CVD), and type 2 diabetes risk factors. In Phase 1 (1992-1997), 855 sedentary subjects from 218 families were recruited and 742 subjects (483 Whites from 99 families, 259 Blacks from 105 families) completed a standardized 20-week exercise-training program. During Phase 2 (1997-2001), a series of non-genetic studies on determinants of cardiorespiratory endurance, and CVD and type 2 diabetes risk factors in the sedentary state and in the response to training were undertaken. Genetic analyses focused on the determination of the heritability levels, and testing for paternal or maternal effects, major gene effects and segregation patterns. A panel of candidate genes was typed for association and linkage studies. A genome-wide scan was performed for the training response of cardiorespiratory endurance and CVD and type 2 diabetes risk factors. The proposed Phase 3 is organized around five specific aims. First, genetic epidemiology questions pertaining to training-related changes in major CVD risk factors will be investigated with special emphasis on Black and White differences. Second, the search for genes and mutations will continue utilizing four strategies: extension of the genome-wide scan including targeted dense SNPs mapping, extension of the skeletal muscle gene expression studies with SAGE, use of the AFLP technique and use of novel statistical methods such as multivariate linkage methods, subgroup analyses, and total genome-wide linkage tests. Third, the genetic and non-genetic determinants of insulin sensitivity, insulin secretion and glucose effectiveness in response to training will be investigated using LONGMOD, an extension of MINMOD currently in development to model longitudinal data more efficiently. Fourth, the nongenetic determinants of the targeted CVD risk factors and their responses to endurance training will be investigated, with emphasis on Black and White differences. Fifth, we will assess whether a closely supervised 20-week period of regular exercise had any long-term effects on habitual physical activity levels and health status. The findings from Phase 3 of the HERITAGE Family Study will provide unique information on the benefits of a physically active lifestyle and on the determinants of the high and low response phenotypes in Blacks and Whites. This application is submitted from the Pennington Biomedical Research Center which also serves as the HERITAGE Consortium Coordinating Center.

HERITAGE 家族研究的目的是记录耐力训练对心血管和代谢的反应，以及遗传因素对心血管疾病 (CVD) 和 2 型糖尿病危险因素伴随反应的影响。 在第一阶段（1992-1997），招募了来自 218 个家庭的 855 名久坐受试者，其中 742 名受试者（来自 99 个家庭的 483 名白人，来自 105 个家庭的 259 名黑人）完成了为期 20 周的标准化运动训练计划。 在第二阶段（1997-2001）期间，进行了一系列关于久坐状态下心肺耐力的决定因素、心血管疾病和2型糖尿病危险因素以及对训练的反应的非遗传研究。 遗传分析的重点是确定遗传力水平，并测试父本或母本效应、主要基因效应和分离模式。 一组候选基因被分类用于关联和连锁研究。 对心肺耐力、CVD 和 2 型糖尿病危险因素的训练反应进行了全基因组扫描。 拟议的第三阶段围绕五个具体目标进行组织。 首先，将调查与主要 CVD 危险因素的训练相关变化有关的遗传流行病学问题，特别强调黑人和白人的差异。 其次，基因和突变的搜索将继续采用四种策略：扩展全基因组扫描，包括靶向密集 SNP 作图、扩展 SAGE 骨骼肌基因表达研究、使用 AFLP 技术以及使用新的统计方法，如多变量连锁方法、亚组分析和全基因组连锁测试。 第三，将使用 LONGMOD 研究胰岛素敏感性、胰岛素分泌和葡萄糖有效性对训练的遗传和非遗传决定因素，LONGMOD 是目前正在开发的 MINMOD 的扩展，旨在更有效地对纵向数据进行建模。 第四，将研究目标CVD风险因素的非遗传决定因素及其对耐力训练的反应，重点是黑人和白人的差异。 第五，我们将评估密切监督的 20 周定期锻炼是否对习惯性身体活动水平和健康状况产生长期影响。 HERITAGE 家庭研究第三阶段的结果将提供有关身体活跃生活方式的好处以及黑人和白人高和低反应表型的决定因素的独特信息。 该申请由彭宁顿生物医学研究中心提交，该中心同时也是 HERITAGE 联盟协调中心。