Document Detail


The Arg389Gly beta1-adrenoceptor gene polymorphism determines contractile response to catecholamines.
MedLine Citation:
PMID:  15564877     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: 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. CONCLUSION: These data indicate that the Arg389Gly beta1AR polymorphism is functionally relevant in vivo and determines contractile responsiveness to catecholamines in humans.
Authors:
Karl La Rosée; Michael Huntgeburth; Stephan Rosenkranz; Michael Böhm; Petra Schnabel
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Pharmacogenetics     Volume:  14     ISSN:  0960-314X     ISO Abbreviation:  Pharmacogenetics     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-26     Completed Date:  2005-04-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9211735     Medline TA:  Pharmacogenetics     Country:  England    
Other Details:
Languages:  eng     Pagination:  711-6     Citation Subset:  IM    
Affiliation:
Klinik III für Innere Medizin, Universität zu Köln, Germany.
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MeSH Terms
Descriptor/Qualifier:
Arginine / genetics*
Catecholamines / physiology*
Echocardiography
Glycine / genetics*
Heart Atria / ultrasonography
Humans
Male
Muscle Contraction / physiology
Polymorphism, Genetic*
Receptors, Adrenergic, beta-1 / chemistry,  genetics*
Chemical
Reg. No./Substance:
0/Catecholamines; 0/Receptors, Adrenergic, beta-1; 56-40-6/Glycine; 74-79-3/Arginine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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