Beta2-adrenergic receptor genotype affects the renin-angiotensin-aldosterone system response to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern.
BACKGROUND
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).


OBJECTIVE
We hypothesized that the DASH diet associates with increased RAAS activity, and genotype status at beta2-AR G46A modifies this response.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sun
Bei
B
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Williams
Jonathan S
JS
Svetkey
Laura P
LP
Kolatkar
Nikheel S
NS
Conlin
Paul R
PR
D000450:Aldosterone / Q000097:blood / Q000235:genetics / Q000652:urine; D000483:Alleles; D001794:Blood Pressure; D004032:Diet; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000178:diet therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D054647:Nutrigenomics; D020641:Polymorphism, Single Nucleotide; D011188:Potassium / Q000652:urine; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012044:Regression Analysis; D012083:Renin / Q000097:blood / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2; D000450:Aldosterone; D012083:Renin; D011188:Potassium