HYPGENE-GENETICS FITNESS OBESITY & RISK OF HYPERTENSION

HYPGENE-遗传学健身肥胖

• 批准号: 7159332
• 负责人: Tuomo Rankinen
• 金额: $ 30.12万
• 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 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7159332
• 关键词: Aerobic; Alleles; Autonomic nervous system; Biomedical Research; Blood Pressure; Blood Vessels; Blood specimen; Body Weight; Body Weight decreased; Candidate Disease Gene; Cardiac; Cardiovascular Diseases; Classification; Clinic; Clinic Visits; Condition; DNA; DNA Sequence; Data; Databases; Development; Diabetes Mellitus; Diagnosis; Disease regression; Environment; Essential Hypertension; Exercise; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genotype; Haplotypes; High Blood Pressure; Hypertension; Incidence; Individual; Institutes; Lead; Linkage Disequilibrium; Logistic Regressions; Longitudinal Studies; Mediating; Methodology; Modeling; Obesity; Participant; Pathway interactions; Phase; Phosphotransferases; Physical activity; Physicians; Physiological; Preventive; Randomized Clinical Trials; Research; Risk; Role; Sample Size; Secondary Prevention; Signaling Molecule; Single Nucleotide Polymorphism; System; Time; Training; Trees; Universities; Variant; Vasodilation; Visit; Washington; Weight; Weight maintenance regimen; base; beta-adrenergic receptor; blood pressure regulation; case control; cohort; enzyme activity; fitness; follow-up; gene interaction; medical examination; normotensive; novel; obesity risk; prospective; sample collection; shear stress; vasoconstriction

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）：HYPGENE 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成果。该研究的目的是调查候选基因中 DNA 序列变异的贡献，以及它们与心肺健康和肥胖的相互作用，对健美操中心纵向研究 (ACLS) 参与者的高血压风险的影响。在第一阶段（截至2003年1月12日），将从ACLS队列中选择1000名受试者，他们在第一次预防性体检时（从01/1987到02/2001）血压正常且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）出现高血压，而另一半则保持正常血压。第二阶段（12/03至11/05），样本量将增加至1500名受试者（750名病例和750名对照）。病例定义为基线时血压正常但在随访期间出现原发性高血压的个体。比较个体是那些在基线时血压也正常并且在随访期间保持正常血压的人。病例对照状态的确定将在受试者回访库珀诊所期间完成。将对候选基因位点中的一组双等位基因单核苷酸多态性进行分型。候选基因的选择是基于它们在与健身和肥胖调节血压相关的生理途径中的假定作用，或者基于先前研究中的联系和关联的证据。这些候选药物包括有助于血管舒张和血管收缩的内皮因子、β-肾上腺素能受体及其激酶（介导自主神经系统对心脏功能和血管张力的影响）、肾素血管紧张素系统以及介导层流剪切应力对血管壁酶活性和基因表达影响的信号分子。逻辑回归模型以及分类和回归树方法将用于分析基因型、健康水平和肥胖的贡献，以及它们之间的相互作用，对高血压风险的影响。 HYPGENE 研究将产生关于遗传因素在心肺健康水平高或低、肥胖或体重正常的情况下对高血压发展的影响的新数据。这些数据最终可能导致在高血压的一级和二级预防中更有效地利用体力活动和体重控制。