S38G single-nucleotide polymorphism at the KCNE1 locus is associated with heart failure
S38G single-nucleotide polymorphism at the KCNE1 locus is associated with heart failure
复制标题
DOI：
10.1016/j.hrthm.2009.11.032
复制
发表时间：
2010-03-01
期刊：
影响因子：
5.5
通讯作者：
Gensini, Gian Franco
中科院分区：
文献类型：
--
作者：
Fatini, Cinzia;Sticchi, Elena;Gensini, Gian Franco
背景：动作电位持续时间的延长是心室心肌衰竭的标志，其主要决定因素是延迟整流钾电流。编码缓慢激活的心脏钾通道(I-ks) β亚基（minK）的KCNE1基因的遗传变异可能损害心肌复极。实验数据显示KCNE1在心力衰竭（HF）中表达较高。目的研究KCNE1 S38G单核苷酸多态性（SNP）与心衰的关系。方法：我们对323名先前调查的患者中的197名和352名年龄和性别相当的健康对照进行了基因分型。这项研究在186名心衰患者和200名年龄和性别相当的健康受试者中进行了重复研究，这些受试者来自意大利比萨国家研究委员会心血管医学部。结果KCNE1 S38G SNP基因型分布和等位基因频率在患者和对照组之间存在显著差异（P = 0.002和P = 0.008）。在对年龄、性别和传统心血管危险因素进行校正后，在显性模型（优势比[OR] = 2.22 [1.23-3.28]; P = 0.008）和加性模型（OR = 2.13 [1.09-4.15]; P = 0.03）下，KCNE1 38G变异与HF易感性显著相关。KCNE1 S38G SNP的基因型分布和等位基因频率在纽约功能心脏协会分类中没有差异（P = 0.4和P = 0.3）。在HF重复研究中，KCNE1 38G等位基因频率显著高于对照组（38G = 0.59 vs. 0.49; P = 0.004）。38G等位基因在隐性下与HF易感性相关(OR[95%可信区间（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）。结论KCNE1 S38G SNP在两个研究人群中与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。
BACKGROUND 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).OBJECTIVE The purpose of this study was to investigate the association between a KCNE1 S38G single-nucleotide polymorphism (SNP) and HF.METHODS 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.RESULTS 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.CONCLUSION 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.