کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2923910 1175889 2010 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
S38G single-nucleotide polymorphism at the KCNE1 locus is associated with heart failure
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
S38G single-nucleotide polymorphism at the KCNE1 locus is associated with heart failure
چکیده انگلیسی

BackgroundProlongation 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 β-subunit (minK) of a slowly activated cardiac potassium channel (Iks), may impair myocardial repolarization. Experimental data demonstrated a higher KCNE1 expression in heart failure (HF).ObjectiveThe purpose of this study was to investigate the association between a KCNE1 S38G single-nucleotide polymorphism (SNP) and HF.MethodsWe 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.ResultsA 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.ConclusionKCNE1 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Heart Rhythm - Volume 7, Issue 3, March 2010, Pages 363–367
نویسندگان
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