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

IntroductionThe ADRB1 389 polymorphism affects responses to the -1 adrenergic receptor ((1)AR) 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 methodsHealthy 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 6mcg/kg/min. Standardized exercise was performed during the last minute of each infusion.ResultsResting heart rate (HR) response to 6mcg/kg/min dobutamine (HR) was 4.7-fold larger in Arg389Arg than in Gly389Gly [(meanSD) 12.95 +/- 6.99, 2.75 +/- 1.65bpm, respectively, P-ANOVA=0.012]. Renin response to dobutamine (Renin) was 3.9-fold greater in Arg389Arg than in Gly389Gly (P-ANOVA=0.032). Among Arg389Gly heterozygotes, HR and Renin were not significantly different from either homozygote group. In multivariate analysis for HR variance, significant contributions were observed for genotype (P=0.011), baseline HR (P=0.011), and borderline effect for sex (P=0.049).ConclusionIn 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.