The Arg389Gly Beta1-Adrenoceptor Polymorphism and Catecholamine Effects on Plasma-Renin Activity

Abstract

Codon 389 beta1AR polymorphism is a determinant not only of hemodynamic effects but also of PRA. Thus, beta1AR polymorphisms may be useful for predicting therapeutic responses to betaAR-blocker treatment.

β-adrenoceptor blocker treatment and the cardiac β-adrenoceptor-G-protein(s)-adenylyl cyclase system in chronic heart failure

“…They might, however, be involved in modifying progression of diseases and may affect drug responses (Small et al 2003;Kirstein and Insel 2004;Leineweber et al 2004;Brodde et al 2006). Thus, recent data indicate that the Arg389Gly β-1 AR polymorphism determines cardiac responses to dobutamine: dobutamine-infusion-evoked increases in heart rate and/or contractility were significantly larger in subjects homozygous for the Arg389 β-1 AR than in subjects with one or two Gly389 alleles (LaRosee et al 2004;Bruck et al 2005). Similarly, dobutamine-caused increases in plasma renin activity (an effect mediated by renal β-1 AR stimulation) were, in Arg389 β-1 AR subjects, significantly larger than in subjects with one or two Gly389 alleles .…”

“…Ordinates Bisoprolol-induced decrease in dobutamine-evoked increases in heart rate (left, in Δ beats/min), contractility (middle, in Δ ms) and plasma renin activity (right, in Δ ng angiotensin I formed ml −1 h −1 ). Modified from Bruck et al (2005) ( Table 2). Nevertheless, it appears to be justified to speculate that it might be possible by assessment of the Arg389Gly β-1 AR polymorphism to predict responses to β-AR agonist (and blocker) treatment: Patients homozygous for the Arg389 β-1 AR polymorphism should be good responders, whereas patients homozygous for the Gly389 β-1 AR polymorphism should be poor or non-responders.…”

The Future of Pharmacogenetics in the Treatment of Heart Failure

“…Arg 389 homozygosity is associated with enhanced chronotropy, contractility and bisoprolol more effectively reduced sympathetic response. Furthermore Arg 389 homozygotes showed increased plasma renin activity suggesting neuro-hormonal cross-talk is also important (33), thus in this instance structural changes here apparently have the expected effect.…”

“…These findings suggest neuro-hormonal interactions are important and considering genotypes across these two systems may allow more effective tailoring of HF therapy (33). Notwithstanding the good evidence for a drug-gene interaction that is more consistent than any other loci in this setting, ACE I/D genotyping still does not guide ACE inhibitor prescription.…”

Pharmacogenomics of Adrenergic Receptors; from Hypertension to Heart Failure

“…In some of these variants, clinical pharmacological studies have demonstrated their association with the alteration in heart rate or blood pressure in response to β-blockers, as shown in Table 1. It should be noted that the association of genetic variants with these parameters are consistently observed in healthy volunteers [54][55][56] but not in the patients with hypertension. The response to β-blockers may be determined not simply by the genetic polymorphisms but by concomitant conditions in hypertension.…”