Association of KCNQ1, KCNE1, KCNH2 and SCN5A polymorphisms with QTc interval length in a healthy population
Association of KCNQ1, KCNE1, KCNH2 and SCN5A polymorphisms with QTc interval length in a healthy population
复制标题
DOI：
10.1038/sj.ejhg.5201489
复制
发表时间：
2005-11-01
影响因子：
5.2
通讯作者：
Guicheney, P
中科院分区：
文献类型：
--
作者：
Gouas, L;Nicaud, V;Guicheney, P
QT间期（QT）反映了心室复极，并根据各种已知因素（如心率、性别和年龄）而变化。然而，QT-RR模式的高受试者内稳定性也表明遗传成分有助于个体QT长度。为了确定编码心脏离子通道的基因中的单核苷酸多态性（SNP）是否与心率校正的QT（QTc）长度相关，我们分析了来自2008名健康受试者的队列的200名受试者的最短和最长QTc。共有17个多态性进行了基因分型，他们都在哈代-温伯格平衡在两组。KCNQ 1110个SNPs的等位基因频率和单倍型频率在两组间均无显著性差异。相比之下，KCNH 2 2690 C（K897 T）和SCN 5A 5457 T（D1819 D）次要等位基因在QTc间期最短的组中的频率显著更高，而KCNE 1 253 A（D85 N）、SCN 5A 1673 G（H558 R）和1141- 3 A次要等位基因在QTc间期最长的组中的频率显著更高。有趣的是，在KCNH 2 2690 A > C SNP和KCNQ 1 2031+932 A > G SNP之间也发现了相互作用，这表明KCNH 2 2690 C等位基因对QTc长度的影响可能发生在特定的遗传背景中。这表明，位于KCNQ 1，KCNE 1，KCNH 2和SCN 5A的遗传决定因素影响健康个体的QTc长度，并可能代表心血管疾病患者心律失常或心脏性猝死的危险因素。
The QT interval (QT) reflects cardiac ventricular repolarization and varies according to various known factors such as heart rate, gender and age. Nevertheless, a high intrasubject stability of the QT-RR pattern also suggests that a genetic component contributes to individual QT length. To determine whether single nucleotide polymorphisms (SNPs) in genes encoding cardiac ion channels were associated with the heartrate corrected QT (QTc) length, we analyzed two groups of 200 subjects presenting the shortest and the longest QTc from a cohort of 2008 healthy subjects. A total of 17 polymorphisms were genotyped; they were all in the Hardy - Weinberg equilibrium in both groups. Neither allele nor haplotype frequencies of the 10 KCNQ1 SNPs showed a significant difference between the two groups. In contrast, KCNH2 2690 C (K897T) and SCN5A 5457 T (D1819D) minor alleles were significantly more frequent in the group with the shortest QTc interval, whereas KCNE1 253 A (D85N), SCN5A 1673 G (H558R) and 1141- 3 A minor alleles were significantly more frequent in the group with the longest QTc interval. Interestingly, an interaction was also found between the KCNH2 2690 A > C SNP and the KCNQ1 2031+932 A > G SNP suggesting that the effect of the KCNH2 2690 C allele on QTc length may occur within a particular genetic background. This suggests that genetic determinants located in KCNQ1, KCNE1, KCNH2 and SCN5A influence QTc length in healthy individuals and may represent risk factors for arrhythmias or cardiac sudden death in patients with cardiovascular diseases.