| The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment. | |
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MedLine Citation:
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PMID: 22703382 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2012-6-16 |
Journal Detail:
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Title: Clinical and experimental pharmacology & physiology Volume: - ISSN: 1440-1681 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-6-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd. |
Affiliation:
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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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