title: Impact of the canine double-deletion β1 adrenoreceptor polymorphisms on protein structure and heart rate response to atenolol, a β1-selective β-blocker.
abstract: OBJECTIVE
  β-Adrenergic receptor antagonists are widely utilized for the management of cardiac diseases in dogs. We have recently identified two deletion polymorphisms in the canine adrenoreceptor 1 (ADRB1) gene.We hypothesized that canine ADRB1 deletions would alter the structure of the protein, as well as the heart rate response to the β-adrenergic receptor antagonist, atenolol. The objectives of this study were to predict the impact of these deletions on the predicted structure of the protein and on the heart rate response to atenolol in a population of healthy adult dogs.
  
  
  METHODS
  Eighteen apparently healthy, mature dogs with (11) and without (seven) ADRB1 deletions were evaluated. The heart rate of the dogs was evaluated with a baseline ambulatory ECG before and 14-21 days after atenolol therapy (1 mg/kg orally q12 h). Minimum, average, and maximum heart rates were compared between groups of dogs (deletions, controls) using an unpaired t-test and within each group of dogs using a paired t-test. The protein structure of ADRB1 was predicted by computer modeling.
  
  
  RESULTS
  Deletions were predicted to alter the structure of the ADRB1 protein. The heart rates of the dogs with deletions were lower than those of the control dogs (the average heart rates were significantly lower).
  
  
  CONCLUSIONS
  ADRB1 deletions appear to have structural and functional consequences. Individual genome-based treatment recommendations could impact the management of dogs with heart disease.
authors.affiliation: aDepartment of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina bDepartment of Clinical Sciences, Washington State University College of Veterinary Medicine, Pullman, Washington, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Meurs
authors.forename: Josh A
authors.initials: JA
authors.lastname: Stern
authors.forename: Yamir
authors.initials: Y
authors.lastname: Reina-Doreste
authors.forename: Brian A
authors.initials: BA
authors.lastname: Maran
authors.forename: Lhoucine
authors.initials: L
authors.lastname: Chdid
authors.forename: Sunshine
authors.initials: S
authors.lastname: Lahmers
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Keene
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Mealey
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000008:administration & dosage* / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography / Q000662:veterinary; D006339:Heart Rate / Q000187:drug effects; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D018342:Receptors, Adrenergic, beta-1; D001262:Atenolol