Polymorphism of the 5'-flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese

Tissue Antigens. 1998 Jun;51(6):605-12. doi: 10.1111/j.1399-0039.1998.tb03002.x.


Polymorphism of the 5'-flanking promoter/enhancer region of the TNF-alpha gene in Japanese is not well understood. To better understand it, we have determined the 1,358 base pair sequence of the 5'-flanking region of the TNF-alpha gene in nine Japanese, and identified three new polymorphisms at positions 1,031 (T to C change, termed as -1,031C), -863 (C to A, -863A), and -857 (C to T, -857T), with the former two in one allele. The level of TNF-alpha production by concanavalin A (Con A)-activated peripheral blood mononuclear cells from the five donors possessing at least one new allele was 1.8-fold higher than that from the remaining four donors with the dominant allele. The transcriptional promoter activity of the 1,031C/-863A or -857T allele in response to Con A stimulation was 2.0 or 1.7-fold higher than that of the dominant allele, respectively. The allele frequencies of -1,031C, -863A, -857T, -308A (G to A), and -238A (G to A) (the latter two were previously reported) in 575 healthy Japanese were 16.0, 14.0, 17.7, 1.7 and 2.0%, respectively. The -1,031C/-863A or -857T allele was in significant linkage disequilibrium with HLA-B61, -B39 and -DRB1*0901, or with HLA-B54, -B35, -B59, and -DRB1*0405, respectively. The newly identified alleles observed in a relatively large proportion of Japanese may be related to differences in levels of TNF-alpha production in immune responses to various stimuli among individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cells, Cultured
  • Concanavalin A / pharmacology
  • Gene Frequency
  • Humans
  • Japan
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Mitogens / pharmacology
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics*


  • Mitogens
  • Tumor Necrosis Factor-alpha
  • Concanavalin A