Savva Jacqueline, Maqbool Azhar, White Hazel L, Galloway Stacey L, Yuldasheva Nadira Y, Ball Stephen G, West Robert M, De Boer Rudolf A, Van Veldhuisen Dirk J, Balmforth Anthony J
Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.
J Card Fail. 2009 Jun;15(5):435-41. doi: 10.1016/j.cardfail.2008.12.005. Epub 2009 Feb 12.
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.
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.
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.
交感神经激活增强在心力衰竭（HF）的发生发展中起核心作用。我们评估了α₂C -肾上腺素能受体（Del322 - 325）多态性单独或与β₁ -肾上腺素能受体（Arg389）多态性联合，二者各自对交感神经功能有已知的独立影响，是否与HF不良事件风险增加相关。
共有526名参与美托洛尔缓释片/长效片充血性心力衰竭随机干预试验研究的患者接受了两种肾上腺素能受体多态性的基因分型。事件组和非事件组之间α₂C基因型的分布相似。然而，在缺血性充血性HF患者中发现Del322 - 325等位基因的患病率降低（P = 0.022）。同时拥有α₂C Del322 - 325和β₁ Arg389等位基因的患者事件风险并未增加。校正混杂变量和β₁ Arg389Gly多态性后，α₂C Del322 - 325为ins/del + del/del且发生事件的比值比为0.89，95%置信区间为0.49 - 1.63，P = 0.715。同样，校正混杂变量和α₂C Del322 - 325多态性后，β₁ Arg389Gly多态性为Arg/Arg或Arg/Gly且发生事件的比值比为1.13，95%置信区间为0.52 - 2.17，P = 0.864。
α₂C Del322 - 325多态性单独或与β₁ Arg389等位基因联合，均与HF不良事件风险增加无关。
