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 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.
Savva
Jacqueline
J
Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.
Maqbool
Azhar
A
White
Hazel L
HL
Galloway
Stacey L
SL
Yuldasheva
Nadira Y
NY
Ball
Stephen G
SG
West
Robert M
RM
De Boer
Rudolf A
RA
Van Veldhuisen
Dirk J
DJ
Balmforth
Anthony J
AJ
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
D018341:Receptors, Adrenergic, alpha-2; D018342:Receptors, Adrenergic, beta-1; D004247:DNA