Polymorphisms of Adrenoceptors are Not Associated With an Increased Risk of Adverse Event in Heart Failure: A MERIT-HF Substudy

BackgroundEnhanced sympathetic activation has a central role in the development of heart failure (HF). We assessed whether the α2C-adrenoceptor (Del322-325) polymorphism exclusively or in combination with a β1-adrenoceptor (Arg389) polymorphism, each with known independent effects on sympathetic function, were associated with an increased risk of adverse events in HF.Methods and ResultsA total of 526 patients enrolled in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure study were genotyped for both adrenoceptor polymorphisms. The distribution of α2C genotypes was similar between the event and nonevent groups. However, a reduced prevalence of the Del322-325 allele was found in individuals with ischemic congestive HF (P = .022). Patients possessing both the α2C Del322-325 and β1 Arg389 alleles had no increased risk of events. Adjusting for confounding variables and the β1 Arg389Gly polymorphism, the odds ratio of being ins/del + del/del for the α2C Del322-325 and having an event was 0.89 with 95% CI 0.49–1.63, P = .715. Similarly, adjusting for confounding variables and the α2C Del322-325 polymorphism the odds ratio of being Arg/Arg or Arg/Gly for the β1 Arg389Gly polymorphism and having an event was 1.13 with 95% CI 0.52–2.17, P = .864.ConclusionsThe α2C Del322-325 polymorphism exclusively or in combination with the β1Arg389 allele is not associated with an increased risk of adverse events in HF.