Polymorphisms of adrenoceptors are not associated with an increased risk of adverse event in heart failure: a MERIT-HF substudy.

Author(s): Savva J, Maqbool A, White HL, Galloway SL, Yuldasheva NY, Ball SG, West RM, De Boer RA, Van Veldhuisen DJ, Balmforth AJ, Merit-HF Study Group

Affiliation(s): Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.

Publication date & source: 2009-06, J Card Fail., 15(5):435-41. Epub 2009 Feb 12.

Publication type: Comparative Study; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Enhanced sympathetic activation has a central role in the development of heart failure (HF). We assessed whether the alpha(2C)-adrenoceptor (Del322-325) polymorphism exclusively or in combination with a beta(1)-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 alpha(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 alpha(2C) Del322-325 and beta(1) Arg389 alleles had no increased risk of events. Adjusting for confounding variables and the beta(1) Arg389Gly polymorphism, the odds ratio of being ins/del + del/del for the alpha(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 alpha(2C) Del322-325 polymorphism the odds ratio of being Arg/Arg or Arg/Gly for the beta(1) Arg389Gly polymorphism and having an event was 1.13 with 95% CI 0.52-2.17, P=.864. CONCLUSIONS: The alpha(2C) Del322-325 polymorphism exclusively or in combination with the beta(1)Arg389 allele is not associated with an increased risk of adverse events in HF.