Role of β1- and α2c-adrenergic receptor polymorphisms and their combination in heart failure:: A case-control study

Background: Adrenergic activation has a central role in the development of HF. The function of the beta(1)- and the alpha(2C)-adrenergic receptors is influenced by gene polymorphisms: the beta(l)Arg389 variant is associated with increased B-1-receptor sensitivity and the alpha(2C)-receptor Del322-325 variant is associated with decreased alpha(2C) receptor function and increased norepinephrine release. We hypothesised that these polymorphisms could influence the prevalence of heart failure. Methods: The role of the beta(1) and alpha(2C)-adrenergic receptor gene polymorphisms as risk factors for heart failure (HF) was assessed in an Italian white Caucasian population using a case-control study design. Genomic DNA was analysed by polymerase chain reaction-restriction fragment length polymorphisin (PCR-RLFP). Results: We compared 260 Caucasian patients with HF and 230 normal subjects. The beta(1)Arg389 allele was frequent both in the patients with HF (69%) and in the normal subjects (73%). The alpha(2C)Del322-325 variant was rare in both groups (9% and 8%, respectively). Patients homozygotes for either the beta(1)Arg389 or the alpha(2C)Del322-325 alleles had no increased risk of HF (odds ratio [OR], 0.8; 95%CI: 0.5- 1.2 and OR, 0.8; 95% CI: 0.4- 1.8, respectively). Patients homozygotes for both the beta(1)Arg389 and the alpha(2C)Del322-325 alleles had no increased risk of HF as well (OR: 0.6; 95% CI: 0.2-2.1). Conclusions: beta(1)-ARs and alpha(2C)-ARs polymorphisms are not associated with an increased risk of HF in an Italian white Caucasian population. (c) 2005 European Society of Cardiology. Published by B.V. All rights reserved.