title: Polymorphisms of adrenoceptors are not associated with an increased risk of adverse event in heart failure: a MERIT-HF substudy.
abstract: 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.
  
  
  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.
authors.affiliation: Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Savva
authors.forename: Azhar
authors.initials: A
authors.lastname: Maqbool
authors.forename: Hazel L
authors.initials: HL
authors.lastname: White
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Galloway
authors.forename: Nadira Y
authors.initials: NY
authors.lastname: Yuldasheva
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ball
authors.forename: Robert M
authors.initials: RM
authors.lastname: West
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: De Boer
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Van Veldhuisen
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Balmforth
mesh_terms: D000368:Aged; D000483:Alleles; D004247:DNA / Q000235:genetics*; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D018341:Receptors, Adrenergic, alpha-2 / Q000097:blood / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index
chemical_list: D018341:Receptors, Adrenergic, alpha-2; D018342:Receptors, Adrenergic, beta-1; D004247:DNA