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PII‐1
Author(s) -
Cheang K. I.,
Vardeny O.,
Zebrack J. S.,
Munger M. A.,
Gilbert E. M.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.126
Subject(s) - terbutaline , carvedilol , metoprolol , medicine , beta blocker , endocrinology , pharmacology , heart failure , genotype , biology , genetics , asthma , gene
BACKGROUND β2‐adrenergic receptor ( ADRB2 ) polymorphisms affect β2‐mediated glucose production by terbutaline. Whether beta‐blockers' effects on β2‐mediated glucose production are affected by ADRB2 polymorphisms is unknown. This study determines the effect of ADRB2 Arg16Gly and Glu27Gln polymorphisms on β2‐mediated glucose dynamics during beta‐blocker titration in heart failure. METHODS From a previous heart failure cohort whose metoprolol or carvedilol were titrated to maximally tolerated doses (up to metoprolol 200mg/d or carvedilol 25mg twice daily) in 5 visits, we analyzed ADRB2 polymorphisms at codons 16 and 27, and glucose AUC0–180min upon a β2‐agonist (terbutaline) infusion in nondiabetic individuals. RESULTS Glucose AUC (mmol/Lx180 min) upon terbutaline infusion decreases as beta‐blocker dosages increase (p=0.0033, repeated measure ANOVA). At baseline, subjects carrying a Glu allele at codon 27 demonstrated lower glucose AUC compared to individuals homozygous for Gln, although this difference was not significant. After maximal beta‐blocker titration, glucose AUC decreased from 5.5±0.2 to 4.9±0.2 in subjects carrying a Glu allele at codon 27 versus from 6.3±0.4 to 5.5±0.4 in subjects homozygous for Gln (p=0.0342, ANCOVA for comparisons between genotype groups). The ADRB2 Arg16Gly variant was not associated with differences in glucose values. CONCLUSIONS ADRB2 polymorphisms may play a role in β2‐mediated glucose production in heart failure patients taking beta‐blockers. Clinical Pharmacology & Therapeutics (2005) 79 , P35–P35; doi: 10.1016/j.clpt.2005.12.126