HYPGENE-GENETICS FITNESS OBESITY & RISK 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项目。本研究的目的是调查候选基因中DNA序列变异的贡献，以及它们与心肺适能和肥胖的相互作用对有氧运动中心纵向研究（ACLS）参与者高血压风险的影响。在第一阶段（截至2003年1月12日），将从ACLS队列中选择一组1000例受试者，这些受试者在首次预防性医学检查时（1987年1月至2001年2月）血压正常且无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（持续时间2至16年）发生高血压，而另一半保持血压正常。在第二阶段（2003年12月至2005年11月），样本量将增加至1500例受试者（750例病例和750例对照）。病例定义为基线时血压正常，但在随访期间发生原发性高血压的个体。对照个体是那些在基线时血压正常并在随访期间保持血压正常的个体。将在受试者返回库珀诊所时确定病例对照状态。将对候选基因位点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有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。候选者包括促进血管舒张和血管收缩的内皮因子、介导自主神经系统对心脏功能和血管张力的影响的β-肾上腺素能受体及其激酶、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的影响的信号分子。将使用逻辑回归模型和分类和回归树方法来分析基因型、健康水平和肥胖以及它们的交互作用对高血压风险的贡献。HYPGENE研究将产生新的数据，说明在高或低心肺健康水平或肥胖或正常体重的情况下，遗传因素对高血压发展的影响。这些数据可能最终导致在高血压的一级和二级预防中更有效地使用体力活动和体重控制。

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.