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The 894G Allele of the Endothelial Nitric Oxide synthase 3 (eNOS) is Associated with Atrial Fibrillation in Chronic Systolic Heart Failure

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.

Results: 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, 1.020.0, p=0.02).

Conclusions: 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.

Credits: Fuad Fares PhD; Yoav Smith PhD; Naiel Azzam PhD; Barak Zafrir MD; Basil S. Lewis, MD, FRCP; Offer Amir, MD

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