Tumor necrosis factor alpha polymorphism in heart failure/cardiomyopathy.
Tumor necrosis factor a (TNF-alpha) is a proinflammatory cytokine that is produced by activated macrophages. It has been shown to stimulate the release of endothelial cytokines and NO, increase vascular permeability, decrease contractility, and induce a prothrombotic state. The most studied TNF-a gene mutation in heart disease is a gamma to alpha substitution, which occurs when 308 nucleotides move upstream from the transcription initiation site in the TNF promoter and has been associated with elevated levels of TNF-alpha. The TNF1 allele (wild type) contains gamma at this site, while the TNF2 allele has an alpha substitution at the site. The TNF2 allele is a more powerful transcriptional activator, therefore leading to higher TNF-alpha levels. Most of the studies to date have failed to conclusively show any link between the polymorphism and heart disease, both coronary artery disease and cardiomyopathy/heart failure.
Vadlamani
Lou
L
Department of Cardiovascular Medicine, Ohio State University, Suite 200, Davis Heart and Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210-1252, USA. vadlamani-1@medctr.osu.edu
Iyengar
Srinivas
S
D000483:Alleles; D009202:Cardiomyopathies / Q000188:drug therapy / Q000235:genetics*; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha