Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy.
Heart Rhythm. 2010 Mar;7(3):363-7. doi: 10.1016/j.hrthm.2009.11.032. Epub 2009 Dec 2.
Prolongation of the action potential duration, whose major determinants are the delayed-rectifier potassium currents, is a hallmark of failing ventricular myocardium. Genetic variants in the KCNE1 gene, encoding for the beta-subunit (minK) of a slowly activated cardiac potassium channel (I(ks)), may impair myocardial repolarization. Experimental data demonstrated a higher KCNE1 expression in heart failure (HF).
The purpose of this study was to investigate the association between a KCNE1 S38G single-nucleotide polymorphism (SNP) and HF.
We genotyped 197 out of 323 previously investigated patients and 352 healthy controls comparable for age and sex. This study was replicated in 186 HF patients and in 200 healthy subjects comparable for age and sex and recruited from the Department of Cardiovascular Medicine of the National Research Council, Pisa, Italy.
A significant difference in genotype distribution and allele frequency between patients and controls was observed for the KCNE1 S38G SNP (P = .002 and P = .0008, respectively). The KCNE1 38G variant was associated with a significant predisposition to HF under a dominant (odds ratio [OR] = 2.22 [1.23-3.28]; P = .008) and additive (OR = 2.13 [1.09-4.15]; P = .03) model, after adjustment for age, sex, and traditional cardiovascular risk factors. No difference in genotype distribution and allele frequency for the KCNE1 S38G SNP according to functional New York Heart Association class was found (P = .4 and P = .3, respectively). In the HF replication study, the KCNE1 38G allele frequency was significantly higher in comparison with that observed in the control population (38G = 0.59 vs. 0.49; P = .004). The 38G allele was associated with HF predisposition under the recessive (OR [95% confidence interval (CI)] = 2.49 [1.45-4.29]; P = .001) and additive models (OR [95% CI] = 2.63 [1.29-5.35]; P = .008), after adjustment for traditional risk factors.
KCNE1 S38G SNP is associated with HF predisposition in two study populations. Nevertheless, further studies performed in larger populations and aimed to better define the role of this locus are required.
动作电位持续时间的延长，其主要决定因素是延迟整流钾电流，是衰竭心室心肌的标志。编码缓慢激活的心肌钾通道（I（ks）的β亚基（minK）的 KCNE1 基因的遗传变异可能会损害心肌复极。实验数据表明心力衰竭（HF）中 KCNE1 的表达更高。
本研究旨在探讨 KCNE1 S38G 单核苷酸多态性（SNP）与 HF 之间的关系。
我们对 197 名先前研究的患者和 352 名年龄和性别相匹配的健康对照者进行了基因分型。这项研究在意大利比萨国家研究委员会心血管医学系招募的 186 名 HF 患者和 200 名年龄和性别相匹配的健康受试者中进行了复制。
在 KCNE1 S38G SNP 中，患者和对照组之间的基因型分布和等位基因频率存在显著差异（P =.002 和 P =.0008）。KCNE1 38G 变体在显性（OR = 2.22 [1.23-3.28]；P =.008）和加性（OR = 2.13 [1.09-4.15]；P =.03）模型下与 HF 显著易感性相关，在调整年龄、性别和传统心血管危险因素后。根据功能性纽约心脏协会分级，KCNE1 S38G SNP 的基因型分布和等位基因频率无差异（P =.4 和 P =.3）。在 HF 复制研究中，与对照组相比，KCNE1 38G 等位基因频率显着升高（38G = 0.59 与 0.49；P =.004）。38G 等位基因在隐性（OR [95%置信区间（CI）] = 2.49 [1.45-4.29]；P =.001）和加性模型（OR [95% CI] = 2.63 [1.29-5.35]；P =.008）下与 HF 易感性相关，在调整传统危险因素后。
KCNE1 S38G SNP 与两个研究人群的 HF 易感性相关。然而，需要在更大的人群中进行进一步的研究，以更好地确定该基因座的作用。
