Effects of a single nucleotide polymorphism on the expression of human tumor necrosis factor-alpha

Abstract

Tumor necrosis factor (TNF)-α plays a prominent role in inflammations and is a proinflammatory cytokine that has been implicated in the pathogenesis of autoimmune and infectious diseases. Recent association studies have found that the TNF-α -857T allele was associated with several disorders. Here we demonstrate, with reporter genes under the control of the two allelic TNF-α promoters, that the minor allele -857T is a much stronger transcriptional activator than the major allele -857C in RAW264.7 cell line in response to lipopolysaccharide stimulation. However, the result was not consistent in HeLa cell line. Furthermore, for the quantitative analysis of TNF-α synthesis between the -857C/C genotype from healthy subjects and the -857C/T genotype from AS patients, the quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were performed separately. There was no significant difference between the two groups at the level of mRNA and protein. These results show that this polymorphism may have a direct effect on TNF-α regulation in a tissue-specific manner, and apart from the polymorphism at -857 in the TNF-α promoter, there may be other factors affecting the expression of TNF-α. © 2006 The Authors.