Mutation Analysis Ion Channel Genes Ventricular Fibrillation Survivors with Coronary Artery Disease

作者：Novotny Tomas^*; Kadlecova Jitka; Raudenska Martina; Bittnerova Alexandra; Andrsova Irena; Florianova Alena; Vasku Anna; Neugebauer Petr; Kozak Milan; Sepsi Milan; Krivan Lubomir; Gaillyova Renata; Spinar Jindrich

来源：Pacing and Clinical Electrophysiology, 2011, 34(6): 742-749.

DOI：10.1111/j.1540-8159.2011.03045.x

• sudden death
• ventricular fibrillation
• ion channel
• mutation

Methods: The entire coding sequence of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes was analyzed in 45 (five females) CAD individuals-survivors of documented VF and in 90 matched healthy controls. In another control group of 141 matched patients with CAD without malignant arrhythmias, the exons containing rare coding variants found in the VF survivors were sequenced.
Results: The carrier frequency of all the rare sequence variants was significantly higher in the VF survivors (8/45, 17.8%) than in CAD controls (3/141, 2.2%, P = 0.001). In VF survivors, four coding variants in eight individuals were found. Three in KCNH2 gene: R148W and GAG186del are novel; P347S was previously related to long QT syndrome. In SCN5A gene, P2006A variant was found in five unrelated males. This variant has been demonstrated previously to have small effect on sodium channel kinetics. No rare coding variants were found in the healthy controls. The P2006A variant was found in three CAD controls.
Conclusion: The prevalence of selected, rare coding variants in five long QT genes was significantly higher in cases versus controls, confirming a mechanistic role for these genes among a subgroup of patients with coronary disease and VF. (PACE 2011; 1-8).

• 出版日期2011-6