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. Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
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 KCNE1S38G 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 KCNE1S38G 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 KCNE1S38G 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:KCNE1S38G 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. Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Authors: John J Ryan; Matthew Kalscheur; Lisa Dellefave; Elizabeth McNally; Stephen L Archer Journal: Int J Cardiol Date: 2011-09-09 Impact factor: 4.164
Authors: Sek Ying Chair; Judy Yuet Wa Chan; Mary Miu Yee Waye; Ting Liu; Bernard Man Hin Law; Wai Tong Chien Journal: Int J Environ Res Public Health Date: 2021-05-31 Impact factor: 3.390
Authors: Claudio de Lucia; Laurel A Grisanti; Giulia Borghetti; Michela Piedepalumbo; Jessica Ibetti; Anna Maria Lucchese; Eric W Barr; Rajika Roy; Ama Dedo Okyere; Haley Christine Murphy; Erhe Gao; Giuseppe Rengo; Steven R Houser; Douglas G Tilley; Walter J Koch Journal: Cardiovasc Res Date: 2022-01-07 Impact factor: 13.081