“Role of the Beta‐adrenergic Receptors in the Cardiac Response to Beta‐blocker Therapy”

Abstract

Arrhythmias are electrical abnormalities leading to irregular heart rhythms. The central nervous system releases endogenous catecholamines, which bind to adrenergic receptors on the heart and may increase the risk of arrhythmias.Patients with arrhythmias treated with â‐blocker therapy result in a significant reduction in the incidence of cardiac events, however, not all patients respond to â‐blocker therapy and the molecular basis is poorly understood in children. Previous studies in adults with heart failure identified S49G and G389R single nucleotide polymorphisms (SNPs) in â‐1ADR associated with the refractoriness using â‐blocker therapy.We sought to investigate whether these SNPs affect â‐blocker therapy in children with arrhythmias. We setup a pilot study to test non‐responsive subjects, responsive individuals, patients with heart diseases without arrhythmias and general control subjects. Polymerase chain reactions were followed by direct DNA sequencing covering the coding sequence of both ADRB1/2 genes. The preliminary screening process identified the S49G and G389R SNPs in the ADBR1, while a novel ADBR2 variant was also identified. We will need to expand the patient cohorts to reach statistical significance. Finding â‐1/2ADR variants in subjects with arrhythmias will greatly help understand the role these receptors play in unsuccessful responsiveness to â‐blocker therapy.