Beta1 and beta2-adrenergic receptor polymorphisms and idiopathic ventricular arrhythmias

Idiopathic ventricular arrhythmias commonly refer to ventricular tachycardia (VT) and/or frequent/monomorphic premature ventricular contractions (PVC) in patients with structurally normal heart. Activation of sympathetic tone has been shown to play an important role in the provocation and maintenance of these arrhythmias. We investigated whether common single nucleotide polymorphisms in the beta(1) and beta(2)-adrenergic receptors are associated with idiopathic ventricular arrhythmias.

A total of 143 unrelated patients presenting with idiopathic ventricular arrhythmias were prospectively included in a case-control association study. Patient population was matched by age and gender to the unrelated, healthy control subjects (N = 307). All study subjects were of Turkish (Anatolian Caucasian) descent. Allele and genotype frequencies of the Gly389Arg and Ser49Gly polymorphisms of the beta(1)-adrenergic receptor and Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms of the beta(2)-adrenergic receptor were compared between patient population and control subjects. The genotype frequencies were in Hardy-Weinberg equilibrium.

Patients with idiopathic ventricular arrhythmias had higher frequency of Arg389Arg genotype (22.4% vs 1.6%, P < 0.001), Arg389Gly49 (5.24% vs 0.73%, P = 0.005), and Arg389Ser49 (36.7% vs 13.6%, P < 0.001) haplotypes of the beta(1)-adrenergic receptor, and higher frequency of Gly16Gly (31.5% vs 13.4%, P < 0.001), Glu27Glu genotypes (18.2% vs 10.1%, P = 0.006) and Gly16Gln27Thr164 (15.3% vs 7.4%, P = 0.002), Gly16Glu27Thr164 (13.1% vs 7%, P = 0.004), and Gly16Glu27Ile164 (13.2% vs 6%, P = 0.002) haplotypes of the beta(2)-adrenergic receptor compared to control subjects.

Our data suggest that common single nucleotide polymorphisms in the beta(1) and beta(2)-adrenergic receptors are significantly associated with idiopathic ventricular arrhythmias in Turkish population.