Tumor Necrosis Factor α Polymorphism in Heart Failure/Cardiomyopathy

Abstract

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.

Long-Term Survival and Apolipoprotein A1 Level in Chronic Heart Failure: Interaction With Tumor Necrosis Factor α −308 G/A Polymorphism

“…Homozygous carriers of TNFa -308 allele A have worse outcomes in infectious diseases such as cerebral malaria and leishmaniasis (Abraham & Kroeger, 1999). Considering the potential role of TNFa in the pathogenesis of heart failure it was hypothesized that TNFa -308 polymorphism may correlate with the presence and severity of the disease (Vadlamani & Iyengar, 2004). Although several studies have been completed in the past, results are not unambiguous whether this correlation exists or not (Vadlamani & Iyengar, 2004).…”

Differential Reactions of Microglia to Brain Metastasis of Lung Cancer

“…TNF-α is a cytokine released by immune cells, including activated microglia. While it can cause cytolysis of certain tumor cell lines, TNF-α can stimulate cell proliferation and induce cell differentiation under certain conditions (35). In the CNS, TNF-α released from reactive microglia (36) or astrocytes (37) could promote neurodegeneration.…”

Pharmacogenetics and the concept of individualized medicine

“…Most of the studies to date have failed to show any link between polymorphism in tumor necrosis factor alpha and both cardiomyopathy and coronary artery disease. 30 However, variation in two genes encoding angiotensin-converting enzyme and endothelial nitric oxide synthase influence the effects of standard therapies. 31 In addition, polymorphism in the sodium channel gammasubunit promoter region is significantly associated with blood pressure response to hydrochlorothiazide.…”