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Effects of sex and the common ADRB1 389 genetic polymorphism on the hemodynamic response to dobutamine

Yogev, Dotana; Basheer, Maamounb; Blotnick, Simchaa; Caraco, Yosepha; Muszkat, Mordechaia

doi: 10.1097/FPC.0000000000000174
ORIGINAL ARTICLES
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Introduction The ADRB1 389 polymorphism affects responses to the β-1 adrenergic receptor (β1AR) agonist in vitro. Previous studies on its effect on the response to dobutamine stress echocardiography were conflicting. In addition, sex differences in the response to dobutamine have been suggested. The aim of this study was to determine whether the ADRB1 389 polymorphism affects the hemodynamic response to dobutamine in healthy individuals including men and women.

Participants and methods Healthy individuals were recruited according to their ADRB1 49 and 389 genotypes [15 Arg389Arg, 10 Gly389Arg, and 10 Gly389Gly individuals, (all Ser49Ser), 21 men and 14 women]. Dobutamine was infused at 2, 4, and 6 mcg/kg/min. Standardized exercise was performed during the last minute of each infusion.

Results Resting heart rate (HR) response to 6 mcg/kg/min dobutamine (ΔHR) was 4.7-fold larger in Arg389Arg than in Gly389Gly [(mean±SD) 12.95±6.99, 2.75±1.65 bpm, respectively, PANOVA=0.012]. Renin response to dobutamine (ΔRenin) was 3.9-fold greater in Arg389Arg than in Gly389Gly (PANOVA=0.032). Among Arg389Gly heterozygotes, ΔHR and ΔRenin were not significantly different from either homozygote group. In multivariate analysis for ΔHR variance, significant contributions were observed for genotype (P=0.011), baseline HR (P=0.011), and borderline effect for sex (P=0.049).

Conclusion In healthy individuals, HR and renin responses to dobutamine were more than three-fold greater among ADRB1 Arg389 compared with Gly389 homozygotes. Future studies on the effect of the ADRB1 389 polymorphism on dobutamine stress echocardiography should compare Arg389 and Gly389 homozygotes.

aDepartment of Medicine, Division of Clinical Pharmacology

bCentral Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

Correspondence to Mordechai Muszkat, MD, Department of Medicine, Division of Clinical Pharmacology, Hadassah-Hebrew University Medical Center, PO Box 12000, Jerusalem 91120, Israel Tel/fax: 972 267 78836; e-mail: muszkatm@hadassah.org.il

Received February 12, 2015

Accepted July 31, 2015

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