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

Background: Enhanced sympathetic activation has a central role in the development of heart failure (HF). We assessed whether the α_2C-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 Results: A 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 α_2C 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 α_2C 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 α_2C 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 α_2C 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. Conclusions: The α_2C Del322-325 polymorphism exclusively or in combination with the β₁Arg389 allele is not associated with an increased risk of adverse events in HF.