ACE GENOTYPE, BP, AND EXERCISE TRAINING IN HYPERTENSIVES

高血压是心血管疾病的主要危险因素。许多基因位点的多态变异会影响一个人的血压(BP)和患高血压的风险。我们的初步数据表明，血管紧张素转换酶(ACE)的正型会影响运动训练高血压患者的收缩和舒张期血压下降。因此，在健康、久坐、中老年、血压正常偏高或高血压1期的受试者中，我们将检验我们的基本假设：在ACE II和ID中，随着运动训练，收缩压和舒张压下降得比ACE DD基因型的个体更大。基于ACE基因的筛查后，受试者将稳定在AHA第一步饮食中。然后，受试者完成基线测试、6个月的运动训练和最终测试。如果VO2max、身体成分或局部脂肪分布在运动训练中在不同的基因型之间发生不同的变化，它们将与初始BP和种族一起包括在模型中，以评估遗传和非遗传变量对运动训练中BP变化的独立影响。探索性分析将确定肾素-血管紧张素系统成分的变化是否会随着运动训练而在不同的基因型组中发生不同的变化。我们的初步数据还表明，载脂蛋白E(APO E)和脂蛋白脂酶(LPL)PUVELL基因对运动训练降低高血压患者的血压有影响。因此，探索性分析将确定APO E3或E4高血压患者的收缩和舒张压是否比APO E2高血压患者的运动训练降低得更多，LPL-/+高血压患者的降压幅度是否比LPL-/-或+/-型高血压患者的更大。与我们的假设一致的结果将确定4000多万患有正常血压偏高或1期高血压的美国人，他们将通过运动训练获得最大的心血管疾病风险降低，从而将运动训练的最佳分层分配给那些受益最大的人。相反，确定哪些高血压患者将通过运动训练减少血压，将使他们能够专注于对他们来说可能更有效的干预措施。在未来，这些结果可能与尚未确定的对药物和其他生活方式干预的最佳BP反应的遗传标记一起用于指导新诊断的高血压患者进行他们对BP和心血管疾病风险控制的最有效干预。

Hypertension is a major risk factor for cardiovascular (CV) disease. Polymorphic variations at numerous gene loci affect a person's blood pressure (BP) and risk of developing hypertension. Our preliminary data suggest that angiotensin converting enzyme (ACE) gentoype affects the systolic and diastolic BP reductions that occur in hypertensives with exercise training. Thus, in healthy, sedentary, middle-aged and older subjects with High Normal BP or Stage 1 Hypertension, we will test our primary hypothesis: Systolic and diastolic BP decrease more with exercise training in ACE II and ID than in ACE DD genotype individuals. After screening based on ACE genotype, subjects will be stabilized on an AHA Step I diet. Subjects then complete Baseline Testing, 6 months of exercise training and Final Testing. If VO2max, body composition, or regional fat distribution change differently among genotypes with exercise training, they will be included, with initial BP and race, in models to assess the independent effects of genetic and non- genetic variables on BP changes with exercise training. Exploratory analyses will determine if changes in renin- angiotensin system components change differently with exercise training among genotype groups. Our preliminary data also indicate that apolipoprotein E (APO E) and lipoprotein lipase (LPL) Pvull genotype affect BP reductions with exercise training in hypertensives. Thus, exploratory analyses will determine if systolic and diastolic BP decrease more with exercise training in APO E3 or E4 than APO E2 hypertensives and more in LPL Pvull +/+ than LPL Pvull -/- or +/- genotype hypertensives. Results consistent with our hypothesis will identify those of the 40 plus million Americans with high normal BP or Stage 1 hypertension who will obtain the greatest CV disease risk reductions with exercise training, resulting in the optimal stratifying of exercise training to those benefiting the most. Conversely, identifying hypertensives who will reduce BP the lease with exercise training would allow them to focus on interventions that might be more efficacious for them. In the future, these results may be used along with yet-to-be-identified genetic markers for optimal BP responses to medications and other lifestyle interventions to direct newly-diagnosed hypertensives to their most efficacious intervention for BP and CV disease risk control.