Sun Bei, Williams Jonathan S, Svetkey Laura P, Kolatkar Nikheel S, Conlin Paul R
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Am J Clin Nutr. 2010 Aug;92(2):444-9. doi: 10.3945/ajcn.2009.28924. Epub 2010 Jun 2.
Beta(2)-adrenergic receptor (beta2-AR) is a susceptibility locus for hypertension, and polymorphisms at this site relate to salt sensitivity and low plasma renin activity (PRA). The Dietary Approaches to Stop Hypertension (DASH) dietary pattern lowers blood pressure and appears to interact with the renin-angiotensin-aldosterone system (RAAS).
We hypothesized that the DASH diet associates with increased RAAS activity, and genotype status at beta2-AR G46A modifies this response.
We genotyped participants in the DASH-Sodium study (n = 372) at beta2-AR G46A to determine the association with blood pressure, RAAS components, and consumption of the DASH diet. We used 2-way mixed linear regression and an additive model for all primary analyses.
Mean (+/-SEM) PRA was significantly higher in participants in the DASH group than in participants in the control group (0.68 +/- 0.03 compared with 0.54 +/- 0.03 ng x mL(-1) x h(-1), P = 0.002). Serum aldosterone, urinary aldosterone, and urinary potassium concentrations were also significantly higher in the DASH group (P < 0.01 for all). We observed significant gene-diet interactions for changes in systolic blood pressure (SBP) and concentrations of aldosterone and urinary potassium (P for interaction = 0.048, 0.017, and 0.001 for SBP and aldosterone and urinary potassium concentrations, respectively). There was an association between the A allele of beta2-AR G46A and greater blood pressure reduction and blunted aldosterone and PRA responses to the DASH diet.
Our results indicate that the DASH diet lowers blood pressure and increases PRA and aldosterone concentrations. There is an association between the G46A polymorphism of beta2-AR and blood pressure and RAAS responses to the DASH diet, which suggests that beta2-AR may be a genetic modifier of DASH-diet responsiveness. This trial was registered at clinicaltrials.gov as NCT00000608.
β₂肾上腺素能受体(β2-AR)是高血压的一个易感基因座,该位点的多态性与盐敏感性及低血浆肾素活性(PRA)相关。终止高血压膳食方法(DASH)饮食模式可降低血压,且似乎与肾素-血管紧张素-醛固酮系统(RAAS)相互作用。
我们假设DASH饮食与RAAS活性增加相关,且β2-AR G46A位点的基因型状态会改变这种反应。
我们对DASH-钠研究中的参与者(n = 372)进行β2-AR G46A基因分型,以确定其与血压、RAAS组分及DASH饮食摄入量之间的关联。所有主要分析均采用双向混合线性回归和加性模型。
DASH组参与者的平均(±SEM)PRA显著高于对照组(分别为0.68±0.03与0.54±0.03 ng·mL⁻¹·h⁻¹,P = 0.002)。DASH组的血清醛固酮、尿醛固酮及尿钾浓度也显著更高(均P < 0.01)。我们观察到收缩压(SBP)变化以及醛固酮和尿钾浓度存在显著的基因-饮食交互作用(SBP、醛固酮和尿钾浓度的交互作用P分别为0.048、0.017和0.001)。β2-AR G46A的A等位基因与更大程度的血压降低以及醛固酮和PRA对DASH饮食的反应减弱相关。
我们的结果表明,DASH饮食可降低血压,并增加PRA和醛固酮浓度。β2-AR的G46A多态性与血压及RAAS对DASH饮食的反应之间存在关联,这表明β2-AR可能是DASH饮食反应性的遗传修饰因子。该试验在clinicaltrials.gov注册,注册号为NCT00000608。