HYPGENE-GENETICS FITNESS OBESITY & RISK OF HYPERTENSION

HYPGENE-遗传学健身肥胖

• 批准号: 6727017
• 负责人: Tuomo Rankinen
• 金额: $ 33.02万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-16 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6727017
• 关键词: aerobic exercise; cardiovascular system; clinical research; cooperative study; disease /disorder prevention /control; disease /disorder proneness /risk; essential hypertension; familial hypertension; gene environment interaction; gene expression; genetic polymorphism; genetic screening; genetic susceptibility; human genetic material tag; human subject; hypertension; longitudinal human study; nucleic acid sequence; obesity; physical fitness; polymerase chain reaction; racial /ethnic difference; single nucleotide polymorphism; statistics /biometry

DESCRIPTION (provided by applicant): The HYPGENE Study is a collaborative effort between the Pennington Biomedical Research Center, the Cooper Institute, and Washington University in St. Louis. The aim of the study is to investigate the contributions of DNA sequence variation in candidate genes as well as their interactions with cardiorespiratory fitness and obesity to the risk of hypertension in participants of the Aerobics Center Longitudinal Study (ACLS). In the first phase (as of 12/01/03), a group of 1000 subjects, who were normotensive and free of cardiovascular disease and diabetes at the time of their first preventive medical examination (from 01/1987 to 02/2001) will be selected from the ACLS cohort. Half of these subjects (n=500) developed hypertension during the follow-up period (duration 2 to 16 years), whereas the other half remained normotensive. In the second phase (from 12/03 to 11/05), the sample size will be increased to 1500 subjects (750 cases and 750 controls). Cases are defined as individuals who were normotensive at baseline but developed essential hypertension during follow-up. Comparison individuals are those who also were normotensive at baseline and remained normotensive during follow-up. The ascertainment of the case-control status will be done during the subjects' return visits to the Cooper Clinic. A panel of biallelic single nucleotide polymorphisms in candidate gene loci will be typed. The candidate genes are selected based on their putative roles in the physiological pathways pertaining to the regulation of blood pressure by fitness and obesity, or on evidence of linkages and associations in previous studies. The candidates include endothelial factors contributing to vasodilation and vasoconstriction, beta-adrenergic receptors and their kinases, which mediate the effects of autonomic nervous system on cardiac function and vascular tone, the reninangiotensin system, and signaling molecules that mediate the effects of laminar shear stress on vascular wall enzyme activity and gene expression. Logistic regression modeling and classification and regression trees methodology will be used to analyze the contribution of genotype, fitness level and obesity, as well as their interactions, to the risk of hypertension. The HYPGENE study will produce novel data on the effects of genetic factors in the presence of either high or low cardiorespiratory fitness level or obesity or normal body weight on the development of hypertension. These data could ultimately lead to more efficient use of physical activity and body weight control in the primary and secondary prevention of hypertension.

描述（由申请人提供）：催眠研究是彭宁顿生物医学研究中心，库珀研究所和圣路易斯华盛顿大学之间的合作努力。该研究的目的是研究候选基因中DNA序列变异的贡献，以及它们与心肺适应性和肥胖症对有氧运动中心纵向研究（ACLS）参与者中高血压风险的相互作用。在第一阶段（截至12/01/03）中，一组1000名受试者在首次预防医学检查时（从01/1987到02/2001），他们具有出色的心血管疾病，没有心血管疾病和糖尿病。这些受试者中有一半（n = 500）在随访期间（2至16年持续时间）出现了高血压，而另一半则保持正常。在第二阶段（从12/03到11/05）中，样本量将增加到1500名受试者（750例和750个对照）。病例被定义为在基线时具有正常性但在随访期间产生必不可少的高血压的个体。比较的人是那些在基线时也具有显着性的人，并且在随访期间保持不正常。确定病例对照状态将在受试者访问库珀诊所的回访期间完成。将键入一组候选基因基因座中的双重单核苷酸多态性。候选基因是根据其在适应性和肥胖对血压调节的生理途径中的推定作用选择的选择，或者是基于先前研究中的联系和关联的证据。候选物包括有助于血管舒张和血管收缩的内皮因素，β-肾上腺素能受体及其激酶，这些因素介导了自主神经系统对心脏功能和血管张力张力的影响，肾血管蛋白系统的影响，以及介导层层压胁迫对层状层次构成eNZeme的影响和依赖eNE的信号分子。逻辑回归建模和分类以及回归树方法将用于分析基因型，健身水平和肥胖症及其相互作用对高血压风险的贡献。催眠研究将在存在高或低心肺适应水平或肥胖或正常体重对高血压发展的情况下的遗传因素影响的新数据中。这些数据最终可能会导致在高血压预防和次要预防中更有效地利用体育活动和体重控制。