Functional effects of β1-adrenoceptor polymorphisms on the hemodynamic response to dobutamine with and without β-blocker administration

Abstract

The relevance of the Arg389Gly- and Ser49Gly-β₁-adrenoceptor (AR) polymorphisms for cardiovascular function and pharmacotherapy is controversial. Out of 38 healthy male volunteers who were screened for both types of the β₁-AR polymorphism 23 subjects underwent dobutamine stress echocardiography at baseline, after administration of metoprolol succinate (n = 18, 190 mg/day) and 44 h after abrupt termination of the β-blocker (n = 17). Heart rate (HR), systolic blood pressure (SAP), HR-corrected left ventricular circumferential fiber shortening (VCF(C)), cardiac output (CO), systemic vascular resistance (SVR) and left ventricular end-systolic meridional wall stress (EsMWS) were measured. β₁-AR gene polymorphisms were analyzed by TaqMan-PCR. Genotype frequency distributions and allele frequencies of the Gly389Arg and Ser49Gly polymorphisms of the β₁-AR were similar to published data. Although body surface area was similar for Arg/Arg subjects and Gly carriers the latter group revealed smaller left ventricular end-diastolic (-0.4 cm, p = 0.04) and end-systolic LV dimensions (-0.4 cm, p = 0.01). During dobutamine stimulation before, during and after termination of metoprolol coadministration no significant effect of the Arg389Gly-β₁-AR polymorphism on HR, SAP, CO and VCF(c) was detected. In contrast, SVR (p = 0.01) and EsMWS (p = 0.04) were significantly higher in Arg/Arg subjects. The VCF(C)-EsMWS regressions were similar for both groups, but revealed a minutely higher baseline contractility in the Arg/Arg group (p < 0.01). The β₁-AR Ser49Gly polymorphism had no effect on any of the measured parameters. Although the Arg389Gly-β₁-AR polymorphism has only minor relevance for LV contractility it may impact left ventricular size and afterload. The Ser49Gly-β₁-AR polymorphism has no relevant effect on LV geometry or function.