title: S38G single-nucleotide polymorphism at the KCNE1 locus is associated with heart failure.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy. cinziafatini@hotmail.com
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fatini
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.forename: Rossella
authors.initials: R
authors.lastname: Marcucci
authors.forename: Valerio
authors.initials: V
authors.lastname: Verdiani
authors.forename: Carlo
authors.initials: C
authors.lastname: Nozzoli
authors.forename: Cristina
authors.initials: C
authors.lastname: Vassallo
authors.forename: Michele
authors.initials: M
authors.lastname: Emdin
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Gensini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D055815:Young Adult
chemical_list: C489622:KCNE1 protein, human; D024642:Potassium Channels, Voltage-Gated