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The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment.
MedLine Citation:
PMID:  22703382     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A gene-drug interaction has been indicated between beta-1 selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). We studied the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR) and the genotype-dependent response to metoprolol and exercise. Twenty-nine healthy male subjects participated in 2 treatment periods (placebo and metoprolol). A 15-min submaximal exercise test was performed after each treatment period, and PRA and HR were measured before and after exercise. Before exercise, median PRA was lower in Gly/Gly subjects than in Arg/Arg subjects after both placebo (P = 0.030) and metoprolol treatment (P = 0.020). After placebo, the exercise-induced PRA increase was greater in Gly/Gly than in Arg/Gly and Arg/Arg subjects (P = 0.033). The linear association between log(PRA) and log(metoprolol concentration) varied significantly between genotypes (P = 0.024). In Gly/Gly subjects, PRA decreased significantly with metoprolol concentration before (P = 0.025) and after exercise (P < 0.001), while in Arg/Gly and Arg/Arg metoprolol concentration had no effect on PRA. The effect of metoprolol concentration on PRA in Gly/Gly subjects was enhanced by exercise (P = 0.044). No significant differences in HR were seen between genotype groups. Resting PRA was lower in Gly/Gly than in Arg/Arg subjects, and the effect of exercise and metoprolol concentration on PRA was stronger in Gly/Gly subjects than with the other two genotypes. Gly/Gly heart failure patients might require lower doses of metoprolol than other patients to block neurohumoral hyperactivity. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.
Authors:
Morten Petersen; Jon T Andersen; Espen Jimenez-Solem; Kasper Broedbaek; Brian R Hjelvang; Trine Henriksen; Erik Frandsen; Julie L Forman; Christian Torp-Pedersen; Lars Køber; Henrik E Poulsen
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-16
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.
Affiliation:
Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100, Copenhagen, Denmark; Department of Clinical Pharmacology, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400, Copenhagen, Denmark; Department of Cardiology, Glostrup Hospital, Nordre Ringvej 57, DK-2600, Glostrup, Denmark.
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