Background: Sustained cardiac adrenergic stimulation has been implicated in the progression of cardiovascular events in patients with dilated cardiomyopathy (DCM). Our group hypothesized that a combination of polymorphisms that result in increased synaptic norepinephrine release and enhanced receptor function would predispose patients with DCM to cardiovascular events. The effect of polymorphisms in adrenergic receptor-related genes on cardiovascular event-free survival in patients with idiopathic DCM was evaluated.
Methods and results: Genotyping at 3 loci (ADRB1 Ser49Gly and Arg389Gly, and NET T-182C) was performed in 83 patients with DCM. Patients were followed prospectively to the endpoint of cardiovascular events (mean follow-up, 45 months). Cardiovascular events were defined as cardiac death and emergent hospitalization as a result of congestive heart failure, arrhythmia, and cerebrovascular events. Analyses were conducted based on the number of predicted risk genotypes a patient carried. The ADRB1 Ser49 allele carrier, ADRB1 Arg389 allele carrier, and NET-182CC genotype were defined as the predicted risk genotypes. Cardiovascular event-free survival was compared based on the number of predicted risk genotypes. Cardiovascular event-free survival was significantly better in patients with fewer than 3 predicted risk genotypes than in those with 3 predicted risk genotypes.
Conclusions: Genotyping at these 3 loci might be a useful approach for identification of patients with DCM at risk for cardiovascular events.