β1-Adrenergic Receptor Polymorphisms and Response to β-Blockade in the African-American Study of Kidney Disease and Hypertension (AASK)

BACKGROUND This study focuses on the relationship between beta(1)-adrenergic receptor (ADRB1) polymorphisms and blood pressure response to the beta-blocker metoprolol among African Americans with early hypertensive nephrosclerosis. METHODS Participants from the African-American Study of Kidney Disease and Hypertension (AASK) trial were genotyped for ADRB1 polymorphisms:Ser49Gly and Arg389Gly. Cox proportional hazards models were used to determine the relationship between ADRB1 polymorphisms and time to reach a mean arterial pressure (MAP) of <= 107 mm Hg in the first year after randomization, adjusted for other predictors of blood pressure response. RESULTS In the Ser49Gly model, Ser49/Gly49 individuals were less responsive compared to Ser49/5er49 only among the more obese (body mass index (BMI)>= kg/m(2)) participants (P < 0.05 for genotype x BMI interaction). The hazard ratio (HR) with a BMI of 39 kg/m(2) was 0.68 (95% confidence interval (CI) 0.46-0.99). In the Arg389Gly model, participants with Arg389 were less likely to respond to metoprolol: HR: 0.68 (95% CI 0.50-0.93). In addition, women were less responsive to metoprolol compared to men: HR: 0.78 (95% CI 0.60-0.995). CONCLUSIONS Ser49/Gly49 was predictive of blood pressure response to metoprolol only among more obese African Americans with early hypertensive nephrosclerosis. In contrast to other studies suggesting increased short-term responsiveness to beta-blockers with Arg389, Arg389 individuals were less responsive in this study analyzing blood pressure over a 1-year period. This may be partly explained by decreased agonist-promoted desensitization with Arg389. However, gender, physiological adaption to stress, interactions between genes and between genes and the environment, as well as study in other patient populations need to be considered.