Gene Polymorphinsms and Prevention of Disability

基因多态性与残疾预防

• 批准号: 6532548
• 负责人: Marco Pahor
• 金额: $ 52.65万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6532548
• 关键词: ACE inhibitors; angiotensin II; arthritis; behavior therapy; body composition; chemotherapy; clinical research; disabling disease; disease /disorder prevention /control; exercise; functional ability; gender difference; gene environment interaction; genetic polymorphism; genotype; geriatrics; human subject; inflammation; medical rehabilitation related tag; muscle strength; nonsteroidal antiinflammatory agent; peptidyl dipeptidase A; performance; phenotype; racial /ethnic difference

One of the primary goals of geriatric medicine is the prevention of age-related disabilities. Physical exercise prevents disability primarily by improving skeletal muscle function. The interaction of genetic factors with behavior and medication use may explain the variability in individual response to the behavioral interventions. Recent evidence suggests that tissue angiotensin II production and the inflammatory response, and possibly the genes that regulate these processes, may play an important role in determining the physical function status. We propose to explore the associations of known and newly identified polymorphisms of the angiotensin converting enzyme (ACE) and cytokines genes with behavior and medication use in determining physical function in older persons. We will use data of the Health And Body Composition (HABC) cohort, and in two randomized trials of behavioral interventions and disability, the Fitness Arthritis and Seniors Trial (FAST) and the Arthritis, Diet and Activity Promotion Trial (ADAPT). These studies offer unique advantages, including the randomized behavioral interventions in the trials and the comprehensive phenotype definition of body composition, muscle performance, disability, disease and inflammation, available in the cohort. Our multidisciplinary team has experts in molecular biology, genetic epidemiology, bioinformatics, geriatrics, body composition, pharmacoepidemiology, biostatistics, and physical exercise and performance assessment. We will recall the FAST and ADAPT participants to collect genetic material and to assess long-term effects of the randomized interventions. We will use stored samples from HABC. We will assess associations of genetic polymorphisms with inflammation, body composition, muscle strength, physical performance and disability, in relation to physical exercise, diet and medication use. The results of the proposed study will provide data on effect size and variability of the association of individual genotypes with the physical function response to behavioral interventions and medication use. We will use the information on the gene polymorphisms, the associated phenotypes, the interventions, the optimal follow-up, and required sample size to design and implement a randomized trial to assess interactions of gene polymorphisms with behavioral and novel pharmacological interventions aimed to prevent the progression of disability by improving muscle strength.

老年医学的主要目标之一是预防与年龄相关的残疾。 体育锻炼主要通过改善骨骼肌功能来预防残疾。 遗传因素与行为和药物使用的相互作用可以解释个体对行为干预的反应的变异性。 最近的证据表明，组织血管紧张素 II 的产生和炎症反应，以及可能调节这些过程的基因，可能在确定身体功能状态中发挥重要作用。 我们建议探索血管紧张素转换酶（ACE）和细胞因子基因的已知和新发现的多态性与确定老年人身体功能的行为和药物使用之间的关联。 我们将使用健康与身体成分 (HABC) 队列的数据，以及两项关于行为干预和残疾的随机试验，即健身关节炎和老年人试验 (FAST) 以及关节炎、饮食和活动促进试验 (ADAPT)。 这些研究提供了独特的优势，包括试验中的随机行为干预以及队列中可用的身体成分、肌肉性能、残疾、疾病和炎症的综合表型定义。 我们的多学科团队拥有分子生物学、遗传流行病学、生物信息学、老年医学、身体成分、药物流行病学、生物统计学、体育锻炼和表现评估方面的专家。 我们将召回 FAST 和 ADAPT 参与者来收集遗传物质并评估随机干预措施的长期效果。 我们将使用 HABC 存储的样本。 我们将评估遗传多态性与炎症、身体成分、肌肉力量、身体表现和残疾以及体育锻炼、饮食和药物使用的关系。 拟议研究的结果将提供有关个体基因型与行为干预和药物使用的身体功能反应之间的效应大小和变异性的数据。我们将利用有关基因多态性、相关表型、干预措施、最佳随访和所需样本量的信息来设计和实施一项随机试验，以评估基因多态性与行为和新型药物干预措施的相互作用，旨在预防通过提高肌肉力量来进展残疾。