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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The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment. / Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen; Broedbaek, Kasper; Hjelvang, Brian R; Henriksen, Trine; Frandsen, Erik; Forman, Julie Lyng; Torp-Pedersen, Christian; Køber, Lars; Poulsen, Henrik Enghusen.
I: Clinical and Experimental Pharmacology and Physiology, Bind 39, Nr. 9, 09.2012, s. 779-785.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment
AU - Petersen, Morten
AU - Andersen, Jon T
AU - Jimenez-Solem, Espen
AU - Broedbaek, Kasper
AU - Hjelvang, Brian R
AU - Henriksen, Trine
AU - Frandsen, Erik
AU - Forman, Julie Lyng
AU - Torp-Pedersen, Christian
AU - Køber, Lars
AU - Poulsen, Henrik Enghusen
N1 - © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
U2 - 10.1111/j.1440-1681.2012.05736.x
DO - 10.1111/j.1440-1681.2012.05736.x
M3 - Journal article
C2 - 22703382
VL - 39
SP - 779
EP - 785
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
SN - 0305-1870
IS - 9
ER -
ID: 40139856