Effects of Tumor Necrosis Factor Gene Polymorphisms on Patients With Congestive Heart Failure

Abstract

Background-Tumor necrosis factor-␣ (TNF-␣) is known to be elevated in patients with congestive heart failure (CHF).Two biallelic polymorphisms have been identified in the TNF gene locus: one in the promoter region of TNF-␣ (TNFA1/2), and the other in the first intron of TNF-␤ (TNFB1/2). Both TNFA2 and TNFB2 alleles are associated with high TNF-␣ production in vitro and susceptibility to inflammatory diseases. Given the importance of TNF-␣ in the pathogenesis of CHF, we studied the prevalence of TNF gene polymorphisms in CHF patients and the correlation of genotypes to in vivo TNF-␣ levels. Methods and Results-TNFA and TNFB genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism technique. There were no differences in the TNF allele frequencies between CHF (nϭ229; TNFA1/2ϭ0.84/0.16, TNFB1/2ϭ0.33/0.67) and control subjects (nϭ139; TNFA1/2ϭ0.84/0.16, TNFB1/2ϭ0.32/0.68). In 211 patients with CHF, circulating levels of TNF-␣ and the soluble receptors type I and type II were measured by ELISA: 6.18Ϯ3.59 pg/mL, 1768Ϯ761 pg/mL, and 4484Ϯ1750 pg/mL, respectively. There were no correlations between TNFA or TNFB genotypes and circulating levels of TNF-␣ or its soluble receptors in the CHF patients. Conclusions-Despite their association with other inflammatory diseases, neither TNFA nor TNFB polymorphisms are related to the presence of CHF or the elevation of circulating TNF-␣. Thus, other factors may be more important in determining the circulating levels of

Is there a future for TNF promoter polymorphisms?

“…A study by Huizinga et al 56 involving 179 subjects used a whole blood LPS stimulation assay, but found no statistical difference dependent on the 308 genotype. Kubota et al 180 analysed circulating levels of TNF in patients with congestive heart failure (n ¼ 211), but could not detect any correlation with TNF genotype. Recently, a study of 129 healthy individuals also failed to detect a difference in TNF production-dependent on genotype.…”

Polymorphisms of Tumor Necrosis Factor-.ALPHA. and Interleukin-10 Genes in Japanese Patients with Idiopathic Dilated Cardiomyopathy.

“…12) The report showed that the TNF-α polymorphism was not related to the presence of congestive heart failure nor the level of circulating TNF-α. Gene polymorphisms have occasionally been variable among the races, so that study might have contained several races.…”

Overexpression of tumor necrosis factor-α increases production of hydroxyl radical in murine myocardium

“…TNF-␣ may play an important role in the pathogenesis of congestive heart failure for the following reasons. First, plasma levels of TNF-␣ are elevated in patients with congestive heart failure (25,28). Second, the failing human heart expresses a substantial amount of TNF-␣ (13,27,35,38).…”