title: β(1)-adrenergic receptor polymorphisms and response to β-blockade in the African-American study of kidney disease and hypertension (AASK).
abstract: BACKGROUND
  This study focuses on the relationship between β(1)-adrenergic receptor (ADRB1) polymorphisms and blood pressure response to the β-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/Ser49 only among the more obese (body mass index (BMI) ≥39 kg/m(2)) participants (P < 0.05 for genotype × 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 β-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.
authors.affiliation: Department of Medicine, University of California, San Diego (UCSD), La Jolla, California, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Lee
authors.forename: Hossein
authors.initials: H
authors.lastname: Aziz
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Michael
authors.initials: M
authors.lastname: Lipkowitz
authors.forename: Daniel T
authors.initials: DT
authors.lastname: O'Connor
authors.forename: Erin
authors.initials: E
authors.lastname: Richard
authors.forename: Victoria
authors.initials: V
authors.lastname: Brophy
authors.forename: Christina L
authors.initials: CL
authors.lastname: Wassel
authors.forename: Roland
authors.initials: R
authors.lastname: Blantz
authors.forename: Vibha
authors.initials: V
authors.lastname: Bhatnagar
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D009400:Nephrosclerosis / Q000235:genetics; D009765:Obesity / Q000235:genetics; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*
chemical_list: C547787:ADRB1 protein, human; D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D008790:Metoprolol