Beta1- and Beta2-adrenergic receptor polymorphisms affect susceptibility to idiopathic dilated cardiomyopathy

OBJECTIVE: β1- and β2-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 β1-AR, and the 5′ leader cistron Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms in the β2-AR. Genotype, allele and haplotype frequencies were analysed. RESULTS: Univariate analysis showed that the distribution of genotype and allele frequencies of the β1-Ser49Gly, β1-Arg389Gly and β2-Arg16Gly polymorphisms was significantly different between the patients and controls, and the β1-Gly49/β1-Arg389 haplotype was significantly more represented in the patients. Multivariate analysis showed that only the β1-Gly49 variant (odds ratio 1.91; 95% confidence interval 1.24-2.95; P = 0.003) and β2-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 β1-AR and the Gly16Gly genotype of the β2-AR were significantly and independently associated with the DCM phenotype, thus suggesting their role in favouring susceptibility to the disease.