• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF(-kappa)B transcription factors.

Tumour necrosis factor-alpha (TNF) expression is increased in inflammatory bowel disease (IBD), and TNF maps to the IBD3 susceptibility locus. Transmission disequilibrium and case-control analyses, in two independent Caucasian cohorts, showed a novel association of the TNF(-857C) promoter polymorphism with IBD (overall P=0.001 in 587 IBD families). Further genetic associations of TNF(-857C) with IBD sub-phenotypes were seen for ulcerative colitis and for Crohn's disease, but only in patients not carrying common NOD2 mutations. The genetic data suggest a recessive model of inheritance, and we observed ex vivo lipopolysaccharide-stimulated whole-blood TNF production to be higher in healthy TNF(-857C) homozygotes. We show the transcription factor OCT1 binds TNF(-857T) but not TNF(-857C), and interacts in vitro and in vivo with the pro-inflammatory NF(-kappa)B transcription factor p65 subunit at an adjacent binding site. Detailed functional analyses of these interactions in gut macrophages, in addition to further genetic mapping of this gene-dense region, will be critical to understand the significance of the observed association of TNF(-857C) with IBD.

Pubmed ID: 12019209


  • van Heel DA
  • Udalova IA
  • De Silva AP
  • McGovern DP
  • Kinouchi Y
  • Hull J
  • Lench NJ
  • Cardon LR
  • Carey AH
  • Jewell DP
  • Kwiatkowski D


Human molecular genetics

Publication Data

May 15, 2002

Associated Grants

  • Agency: NEI NIH HHS, Id: EY15652

Mesh Terms

  • Animals
  • COS Cells
  • Case-Control Studies
  • Cercopithecus aethiops
  • Genes, Reporter
  • Homozygote
  • Humans
  • Inflammatory Bowel Diseases
  • NF-kappa B
  • Organic Cation Transporter 1
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Tumor Necrosis Factor-alpha