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, 1.0‒20.0, 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
Credits: Fuad Fares PhD; Yoav Smith PhD; Naiel Azzam PhD; Barak Zafrir MD; Basil S. Lewis, MD, FRCP; Offer Amir, MD