Fuad Fares1, Yoav Smith2, Naiel Azzam1, Barak Zafrir3,4, Basil S Lewis3, Offer Amir3,4. 1. Department of Human Biology, Faculty of Natural Sciences, University of Haifa and Department of Molecular Genetics, Carmel Medical Center, Haifa, Israel. 2. Genomic Data Analysis Unit, Hadassah Medical School, Hebrew University of Jerusalem, Israel. 3. Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, and Ruth and Bruce Rappaport School of Medicine, Technion‒Israel Institute of Technology, Haifa, Israel. 4. Heart Failure Center, Lin Medical Center, Haifa, Israel.
Abstract
BACKGROUND: Atrial fibrillation (AF) in patients with heart failure signals poor prognosis. The endothelial nitric oxide synthase (eNOS) enzyme is a key player in the counterregulation of oxidative stress, which is related in part to AF pathogenesis. The purpose of this study was to investigate a possible clinical association in heart failure patients between the presence of exon 7 G894T eNOS polymorphism, known to result in the Glu298Asp protein variant, and the occurrence of AF. METHODS: We analyzed the DNA of 344 patients with chronic systolic heart failure for exon 7 G894T eNOS polymorphism, using PCR. Odds ratios for AF were calculated for the homo- and heterozygous G-allele G894T variants relative to the TT variant. RESULTS: Of the 344 patients, 204 (59%) were homozygous for the G allele, 122 (36%) were heterozygous (GT), and 18 (5%) were homozygous for the T allele. AF episodes were documented in 73 patients (36%) with the GG genotype, in 35 (29%) with GT, and in 2 (11%) with TT. The odds ratio for AF, based on the presence of at least one G allele in the eNOS 894 gene, was 3.96 (95% confidence interval, 1.17‒13.56, p=0.04). Having two G alleles increased the odds ratio to 4.5 (95% confidence interval, 1.0‒20.0, p=0.02). CONCLUSION: Patients with systolic heart failure demonstrate strong correlation between AF and the presence of a G allele in the exon 7 G894T eNOS genotype. These findings support the importance of eNOS polymorphism in the pathogenesis of AF in heart failure patients.
BACKGROUND:Atrial fibrillation (AF) in patients with heart failure signals poor prognosis. The endothelial nitric oxide synthase (eNOS) enzyme is a key player in the counterregulation of oxidative stress, which is related in part to AF pathogenesis. The purpose of this study was to investigate a possible clinical association in heart failurepatients between the presence of exon 7 G894TeNOS polymorphism, known to result in the Glu298Asp protein variant, and the occurrence of AF. METHODS: We analyzed the DNA of 344 patients with chronic systolic heart failure for exon 7 G894TeNOS polymorphism, using PCR. Odds ratios for AF were calculated for the homo- and heterozygous G-allele G894T variants relative to the TT variant. RESULTS: Of the 344 patients, 204 (59%) were homozygous for the G allele, 122 (36%) were heterozygous (GT), and 18 (5%) were homozygous for the T allele. AF episodes were documented in 73 patients (36%) with the GG genotype, in 35 (29%) with GT, and in 2 (11%) with TT. The odds ratio for AF, based on the presence of at least one G allele in the eNOS 894 gene, was 3.96 (95% confidence interval, 1.17‒13.56, p=0.04). Having two G alleles increased the odds ratio to 4.5 (95% confidence interval, 1.0‒20.0, p=0.02). CONCLUSION:Patients with systolic heart failure demonstrate strong correlation between AF and the presence of a G allele in the exon 7 G894TeNOS genotype. These findings support the importance of eNOS polymorphism in the pathogenesis of AF in heart failurepatients.
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