Document Detail


Relation of ADRB1, CYP2D6, and UGT1A1 polymorphisms with dose of, and response to, carvedilol or metoprolol therapy in patients with chronic heart failure.
MedLine Citation:
PMID:  20643254     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The response to beta blockers in patients with heart failure could be associated with the genotype of drug-metabolizing enzymes and/or drug targets. The purpose of the present study was to determine whether specific genetic polymorphisms in ADRB1 (encoding the beta1-adrenergic receptor), CYP2D6, and UGT1A1 correlated with dose of, or response to, metoprolol or carvedilol treatment in patients with heart failure. A cohort of patients with heart failure (n = 93), characterized as responders or nonresponders to metoprolol (n = 19) or carvedilol (n = 74) therapy, was retrospectively identified. Individual genotyping was performed for a panel of polymorphisms in the ADRB1, CYP2D6, and UGT1A1 genes. Univariate and multivariate analyses were performed to compare the genotype to the metoprolol or carvedilol response status and dose. A nonresponse was identified in 10 of 19 patients taking metoprolol and 32 of 74 patients taking carvedilol. None of the polymorphisms in ADRB1, CYP2D6, and UGT1A1 were associated with a response or nonresponse. However, a significant relation between the carvedilol (but not metoprolol) dose and the ADRB1 and CYP2D6 genotype was observed. Patients homozygous for the ADRB1 389Gly variant or who were CYP2D6 poor metabolizers achieved a significantly higher dose of carvedilol (p = 0.01 and p = 0.02, respectively). In conclusion, polymorphisms in ADRB1, CYP2D6, and UGT1A1 were not associated with a response to metoprolol or carvedilol therapy in our cohort of patients with heart failure. The ADRB1 and CYP2D6 genotype, alone and in haplotype, were significantly associated with the dose of carvedilol.
Authors:
Linnea M Baudhuin; Wayne L Miller; Laura Train; Sandra Bryant; Karen A Hartman; Mary Phelps; Mary Larock; Allan S Jaffe
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The American journal of cardiology     Volume:  106     ISSN:  1879-1913     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-20     Completed Date:  2010-08-12     Revised Date:  2014-03-28    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  402-8     Citation Subset:  AIM; IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / administration & dosage*
Aged
Alleles
Carbazoles / administration & dosage*
Chronic Disease
Comorbidity
Cytochrome P-450 CYP2D6 / genetics*
Genotype
Glucuronosyltransferase / genetics*
Haplotypes
Heart Failure / drug therapy*,  genetics*,  therapy
Humans
Linear Models
Metoprolol / administration & dosage*
Middle Aged
Phenotype
Polymerase Chain Reaction
Polymorphism, Genetic*
Propanolamines / administration & dosage*
Receptors, Adrenergic, beta-1 / genetics*
Treatment Outcome
Chemical
Reg. No./Substance:
0/ADRB1 protein, human; 0/Adrenergic beta-Antagonists; 0/Carbazoles; 0/Propanolamines; 0/Receptors, Adrenergic, beta-1; 0K47UL67F2/carvedilol; EC 1.14.14.1/Cytochrome P-450 CYP2D6; EC 2.4.1.-/UGT1A1 enzyme; EC 2.4.1.17/Glucuronosyltransferase; GEB06NHM23/Metoprolol

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


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