Relation of ADRB1, CYP2D6, and UGT1A1 polymorphisms with dose of, and response to, carvedilol or metoprolol therapy in patients with chronic heart failure

Linnea M. Baudhuin, Wayne L. Miller, Laura Train, Sandra Bryant, Karen A. Hartman, Mary Phelps, Mary LaRock, Allan S Jaffe

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The response to β 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 β1-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.

Original languageEnglish (US)
Pages (from-to)402-408
Number of pages7
JournalAmerican Journal of Cardiology
Volume106
Issue number3
DOIs
StatePublished - Aug 1 2010

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Cytochrome P-450 CYP2D6
Metoprolol
Heart Failure
Genotype
Therapeutics
carvedilol
Genetic Polymorphisms
Pharmaceutical Preparations
Adrenergic Receptors
Haplotypes
Multivariate Analysis
Enzymes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Relation of ADRB1, CYP2D6, and UGT1A1 polymorphisms with dose of, and response to, carvedilol or metoprolol therapy in patients with chronic heart failure. / Baudhuin, Linnea M.; Miller, Wayne L.; Train, Laura; Bryant, Sandra; Hartman, Karen A.; Phelps, Mary; LaRock, Mary; Jaffe, Allan S.

In: American Journal of Cardiology, Vol. 106, No. 3, 01.08.2010, p. 402-408.

Research output: Contribution to journalArticle

Baudhuin, Linnea M. ; Miller, Wayne L. ; Train, Laura ; Bryant, Sandra ; Hartman, Karen A. ; Phelps, Mary ; LaRock, Mary ; Jaffe, Allan S. / Relation of ADRB1, CYP2D6, and UGT1A1 polymorphisms with dose of, and response to, carvedilol or metoprolol therapy in patients with chronic heart failure. In: American Journal of Cardiology. 2010 ; Vol. 106, No. 3. pp. 402-408.
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abstract = "The response to β 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 β1-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.",
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