β1- and β2-adrenergic receptor polymorphisms affect susceptibility to idiopathic dilated cardiomyopathy

Objective beta(1)- and beta(2)-adrenergic receptors (ARs) play a pivotal role in myocardial function. We investigated whether functionally relevant polymorphisms within the genes encoding for these receptors indicate susceptibility to idiopathic dilated cardiomyopathy (DCM). Methods This case-control association study involved 189 patients with DCM and 378 gender- and age-matched control subjects. All of the subjects were characterised by polymerase chain reaction-restriction fragment length polymorphism analysis in terms of Ser49Gly and Arg389Gly polymorphisms in the beta(1)-AR, and the 5' leader cistron Arg19Cys, Arg16Gly, Gln27Glu, and Thr164lle polymorphisms in the beta(2)-AR. Genotype, allele and haplotype frequencies were analysed. Results Univariate analysis showed that the distribution of genotype and allele frequencies of the beta(1)-Ser49Gly, beta(1)-Arg389Gly and beta(2)-Arg16Gly polymorphisms was significantly different between the patients and controls, and the beta(1)-Gly49/beta(1)-Arg389 haplotype was significantly more represented in the patients. Multivariate analysis showed that only the beta(1)-Gly49 variant (odds ratio 1.91; 95% confidence interval 1.24-2.95; P = 0.003) and beta(2)-Gly16Gly genotype (odds ratio 1.58; 95% confidence interval 1.10-2.26; P = 0.013) carriers were at significantly higher risk of developing DCM. Conclusions In our population from southern Italy, the Gly49 allele of the beta(1)-AR and the Gly16Gly genotype of the beta(2)-AR were significantly and independently associated with the DCM phenotype, thus suggesting their role in favouring susceptibility to the disease.