A polymorphism of the endothelial nitric oxide synthase promoter is associated with an increase in autonomic imbalance in patients with congestive heart failure.
BACKGROUND
In addition to its well-recognized role in the regulation of vascular tone, nitric oxide modulates sympathetic and parasympathetic nervous system activities. Abnormalities of both autonomic control and nitric oxide synthase activity are known to occur in patients with congestive heart failure. Recently, a polymorphism of the promoter of the endothelial nitric oxide synthase (eNOS) gene has been associated with a reduction of eNOS activity. This study tested the hypothesis that patients with congestive heart failure who are homozygous for this polymorphism will have a more advanced imbalance of autonomic activity.


METHODS
Patients who have congestive heart failure were tested for the presence of an eNOS promoter polymorphism (thymidine to cytosine transition [T(-786)C]). Spectral analysis of heart rate variability was performed to quantify sympathetic and parasympathetic autonomic activity, which were compared between subjects homozygous for the polymorphism and all other subjects.


RESULTS
Patients homozygous for the polymorphism of the eNOS promoter had a greater autonomic imbalance as reflected by significant differences in high- and low-frequency heart rate variability. These differences in autonomic function were noted in the absence of intergroup differences in patterns of respiratory variability, demographic features, and despite a higher mean ejection fraction in patients homozygous for the polymorphism.


CONCLUSIONS
Patients with congestive heart failure who are homozygous for this polymorphism of the eNOS promoter were found to have a more advanced autonomic imbalance. This polymorphism may serve as a marker for patients at increased risk for sudden death and more rapid progression of disease.
Binkley
Philip F
PF
Division of Cardiovascular Medicine, Ohio State University, Columbus, Ohio, USA. binkley-1@medctr.osu.edu
Nunziatta
Enrico
E
Liu-Stratton
Yiwen
Y
Cooke
Glen
G
D001341:Autonomic Nervous System / Q000503:physiopathology*; D005260:Female; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012143:Respiratory Physiological Phenomena
C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III