Effects of tumor necrosis factor gene polymorphisms on patients with congestive heart failure

Abstract

Background-Tumor necrosis factor-α (TNF-α) 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-α (TNFA1/2), and the other in the first intron of TNF-β (TNFB1/2). Both TNFA2 and TNFB2 alleles are associated with high TNF-α production in vitro and susceptibility to inflammatory diseases. Given the importance of TNF-α 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-α 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 (n=229; TNFA1/2=0.84/0.16, TNFB1/2=0.33/0.67) and control subjects (n=139; TNFA1/2=0.84/0.16, TNFB1/2=0.32/0.68). In 211 patients with CHF, circulating levels of TNF-α and the soluble receptors type I and type II were measured by ELISA: 6.18±3.59 pg/mL, 1768±761 pg/mL, and 4484±1750 pg/mL, respectively. There were no correlations between TNFA or TNFB genotypes and circulating levels of TNF-α 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-α. Thus, other factors may be more important in determining the circulating levels of TNF-α in CHF.