title: The Arg389Gly beta1-adrenoceptor gene polymorphism determines contractile response to catecholamines.
abstract: OBJECTIVE
  Recently, the Arg389Gly beta1-adrenoceptor (beta1AR) gene polymorphism has been detected. The Arg variant exhibited increased responsiveness to agonist-induced stimulation in vitro. Functional studies in isolated human atrial muscle strips and in-vivo studies revealed contradictory results regarding the functional relevance of this polymorphism. We sought to characterize the functional consequences of the Arg389Gly beta1-AR polymorphism in 30 consecutive healthy male volunteers in vivo.
  
  
  METHODS
  beta1-AR genotype was determined by PCR and restriction analysis, which was confirmed by DNA sequencing. We compared heart rate, blood pressure, and contractile response of the various genotype carriers with a modified dobutamine stress echocardiography protocol.
  
  
  RESULTS
  Subjects homozygous for the Arg389 beta1AR showed a significantly higher increase in fractional shortening upon cumulative doses of dobutamine as compared to subjects carrying one or two copies of the Gly389 allele. A statistically significant difference was observed at a dobutamine dose of 10 microg/kg/min (46.5 +/- 1.3 vs. 41.8 +/- 1.0 %; P = 0.023) and was maximal at 40 microg/kg/min (61.9 +/- 1.4 vs. 52.8 +/- 1.6; P = 0.001). As a result, the systolic blood pressure response to dobutamine was significantly enhanced in individuals homozygous for the Arg389 allele, whereas the effect on heart rate did not differ between the two groups. Normalization for changing afterload conditions by calculating the pressure-dimension ratio revealed similar effects, indicating that the beta1AR-mediated effects are mainly a result of increased myocardial inotropy.
  
  
  CONCLUSIONS
  These data indicate that the Arg389Gly beta1AR polymorphism is functionally relevant in vivo and determines contractile responsiveness to catecholamines in humans.
authors.affiliation: Klinik III für Innere Medizin, Universität zu Köln, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: La Rosée
authors.forename: Michael
authors.initials: M
authors.lastname: Huntgeburth
authors.forename: Stephan
authors.initials: S
authors.lastname: Rosenkranz
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Petra
authors.initials: P
authors.lastname: Schnabel
mesh_terms: D001120:Arginine / Q000235:genetics*; D002395:Catecholamines / Q000502:physiology*; D004452:Echocardiography; D005998:Glycine / Q000235:genetics*; D006325:Heart Atria / Q000000981:diagnostic imaging; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000737:chemistry / Q000235:genetics*
chemical_list: D002395:Catecholamines; D018342:Receptors, Adrenergic, beta-1; D001120:Arginine; D005998:Glycine