Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos 2350, Sala 2061, Porto Alegre, RS 90035-003, Brazil.
Europace. 2010 May;12(5):686-91. doi: 10.1093/europace/euq040. Epub 2010 Feb 25.
We investigated whether the combination of beta(1)-Gly389Arg and GNB3 C825T, two genetic polymorphisms strictly related to adrenergic system modulation, could act as predictors of appropriate therapies in patients with heart failure (HF) using implantable cardioverter-defibrillators (ICDs).
Patients with HF and ICD implantation for primary and secondary prevention were studied. All ICD therapies were registered and classified as appropriate (secondary to ventricular tachycardia) or inappropriate (others). Genetic analysis was performed by polymerase chain reaction and restriction fragment length polymorphism methods. Seventy-three patients with mean left ventricular ejection fraction of 35 +/- 11% were evaluated. Overall, 35 ICD therapies occurred during follow-up in 31 (42.5%) patients. Twenty-four therapies (33%) were appropriate, and 11 (15%) were inappropriate. Individual analysis of each polymorphism only identified T825 carriers of GNB3 C825T as predictor of appropriate shocks. The combined presence of risk genotypes (Arg389 of the beta(1)-Gly389Arg and T825 of the GNB3 C825T) identified patients with higher risk of appropriate shocks. Patients with two at-risk genotypes had a survival rate free of appropriate shocks lower than those with none or only one of these markers (87 vs. 54%, respectively; log-rank statistic = 0.006). Using a Cox regression model, each at-risk genotype was associated with an increment of risk of appropriate ICD shocks (odds ratio = 3.9, 95% confidence interval of 1.3-12.0; P = 0.02).
Genetic polymorphisms of the adrenergic system may help to identify HF patients who are more likely to receive appropriate ICD therapies. Further studies are necessary to determine the clinical applicability of these polymorphisms as predictors of arrhythmias.
我们研究了两种严格与肾上腺素能系统调节相关的遗传多态性β1-Gly389Arg 和 GNB3 C825T 的联合，是否可以作为使用植入式心脏复律除颤器（ICD）治疗心力衰竭（HF）患者的适当治疗的预测因子。
研究了 HF 患者和因原发性和继发性预防而植入 ICD。所有 ICD 治疗均被记录并分类为适当（继发于室性心动过速）或不适当（其他）。通过聚合酶链反应和限制性片段长度多态性方法进行基因分析。73 例患者平均左心室射血分数为 35±11%。总的来说，31 例（42.5%）患者在随访期间发生了 35 次 ICD 治疗。24 次治疗（33%）是适当的，11 次（15%）是不适当的。对每种多态性的单独分析仅确定 GNB3 C825T 的 T825 携带者是适当冲击的预测因子。β1-Gly389Arg 的风险基因型（Arg389）和 GNB3 C825T 的 T825 的联合存在确定了具有更高适当冲击风险的患者。具有两种风险基因型的患者的无适当冲击生存率低于那些无或仅有这些标志物之一的患者（分别为 87%和 54%；对数秩统计=0.006）。使用 Cox 回归模型，每个风险基因型与适当 ICD 冲击的风险增加相关（优势比=3.9，95%置信区间为 1.3-12.0；P=0.02）。
肾上腺素能系统的遗传多态性可能有助于识别更有可能接受适当 ICD 治疗的 HF 患者。需要进一步的研究来确定这些多态性作为心律失常预测因子的临床适用性。
