Identification of three new single nucleotide polymorphisms in the human tumor necrosis factor-alpha gene promoter

Tissue Antigens. 1998 Oct;52(4):359-67. doi: 10.1111/j.1399-0039.1998.tb03056.x.


We have identified three new human tumor necrosis factor-alpha (TNF-alpha) promoter polymorphisms with single nucleotide (nt) substitutions at -862, -856, and -574 nt relative to the TNF-alpha transcription start site. The -862 and -856 nt TNF-alpha promoter polymorphisms occur with high frequency in Caucasian and Cambodian individuals and are each non-randomly associated with three extended HLA haplotypes. This study, in which 61 independent TNF-alpha promoters were analyzed spanning from -977 to +93 nt relative to the TNF-alpha mRNA cap site, establishes a new canonical TNF-alpha promoter sequence. Furthermore, we show that none of the three novel polymorphisms at -862, -856 and -574 nt or polymorphisms previously described at positions -238, -308 and +70 have an effect upon TNF-alpha gene expression in activated lymphocytes. Thus, these TNF-alpha promoter polymorphisms likely serve as markers for neighboring genes encoding HLA or other undefined molecules in the MHC that may influence disease susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cambodia
  • Cell Line
  • Genetic Predisposition to Disease / genetics
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Major Histocompatibility Complex / genetics
  • Mice
  • Molecular Sequence Data
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / genetics*
  • White People / genetics


  • Tumor Necrosis Factor-alpha