title: Beta1-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to beta-blocker therapy.
abstract: OBJECTIVE
  Large variability exists in the improvement in left ventricular (LV) function from beta-blocker treatment. We hypothesized that polymorphisms at codon 389 (Arg389Gly) and 49 (Ser49Gly) in the beta1-adrenergic receptor (AR) gene were associated with LV reverse remodeling changes in response to beta-blocker therapy among heart failure patients.
  
  
  METHODS
  We prospectively enrolled 61 beta-blocker naive patients with systolic heart failure. Patients underwent baseline echocardiography followed by metoprolol CR/XL. The dose was doubled on a biweekly basis up to 200 mg/day or attainment of maximum tolerated dose. Echocardiography was repeated after the patient received the target or highest tolerated dose for 3 months.
  
  
  RESULTS
  Among patients with the Arg389Arg genotype, ejection fraction (EF) increased from 23+/-5 to 29+/-10 (P=0.008). Gly389 carriers did not demonstrate any significant change in EF (22+/-9 to 23+/-11; P=0.45). There was a significant between-group difference in EF by genotype (P=0.04). The Arg389Arg genotype was also associated with significantly greater reductions in LV end-diastolic and end-systolic diameters compared to Gly389 carriers. Patients with the Gly49 variant also had a significantly greater reduction in LV end-diastolic diameter compared to Ser49 homozygotes. Multiple regression analysis modeling revealed that the codon 389 polymorphism was a significant predictor of an improvement in EF and both codon 49 and 389 polymorphisms were significant predictors of final LV end-diastolic diameter.
  
  
  CONCLUSIONS
  Heart failure patients with the Arg389Arg genotype and Gly49 carriers had greater improvements in LV remodeling from beta-blocker treatment.
authors.affiliation: Department of Pharmacy Practice, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Terra
authors.forename: Karen K
authors.initials: KK
authors.lastname: Hamilton
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Pauly
authors.forename: Craig R
authors.initials: CR
authors.lastname: Lee
authors.forename: J Herbert
authors.initials: JH
authors.lastname: Patterson
authors.forename: Kirkwood F
authors.initials: KF
authors.lastname: Adams
authors.forename: Richard S
authors.initials: RS
authors.lastname: Schofield
authors.forename: Bernadette S
authors.initials: BS
authors.lastname: Belgado
authors.forename: James A
authors.initials: JA
authors.lastname: Hill
authors.forename: Juan M
authors.initials: JM
authors.lastname: Aranda
authors.forename: Hossein N
authors.initials: HN
authors.lastname: Yarandi
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D003062:Codon; D004452:Echocardiography; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011941:Receptors, Adrenergic / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D012044:Regression Analysis; D013599:Systole; D013997:Time Factors; D020257:Ventricular Remodeling
chemical_list: D000319:Adrenergic beta-Antagonists; D003062:Codon; D011941:Receptors, Adrenergic; D018342:Receptors, Adrenergic, beta-1