KCNE5 Polymorphism rs697829 is Associated with QT Interval and Survival in Acute Coronary Syndromes Patients

Abstract

KCNE5 Gene Variant, QTc and Survival in ACS. Introduction: The KCNE family is a group of small transmembrane channel proteins involved in potassium ion (K(+) ) conductance. The X-linked KCNE5 gene encodes a regulator of the K(+) current mediated by the potassium channel KCNQ1. Polymorphisms in KCNE5 have been associated with altered cardiac electrophysiological properties in human studies. We investigated associations of the common rs697829 polymorphism from KCNE5 with baseline characteristics, baseline electrocardiographic (ECG) measurements, and patient survival in a cohort of post-acute coronary syndromes (ACS) patients (the Coronary Disease Cohort Study cohort). Methods and Results: DNA samples (n = 1,740) were genotyped for rs697829 using a TaqMan assay. Baseline ECG data revealed corrected QT (QTc) interval was associated with rs697829 in male, but not female, patients, being extended in the G genotype group (A 416 ± 1.71; G 431 ± 4.25 ms, P = 0.002). Covariate-adjusted survival was poorest in G genotype patients in Cox proportional hazard modeling of mortality data of males (P(overall) = 0.020). Male patients with G genotype had a hazard ratio of 1.44 (1.11-2.33) for death when compared to the A genotype male patients (P = 0.048) after adjustment for age, baseline log-transformed N-terminal pro-B-type natriuretic peptide (NTproBNP), β-blocker and insulin treatment, QTc interval, history of myocardial infarction, and physical activity score. Conclusion: This study suggests an association between rs697829, a common single nucleotide polymorphism (SNP) from KCNE5, and ECG measurements and survival in postacute ACS patients. Prolonged subclinical QT interval may be a marker of adverse outcome in this group of patients.