Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus Academic Article


  • Nature Genetics


  • Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 × 10(-8), odds ratio = 1.70) and Korean (P = 8.33 × 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-κB subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.


publication date

  • 2011/3/1


  • 43


  • Antibodies
  • Autoimmune Diseases
  • Enzymes
  • Haplotypes
  • Inflammation
  • Messenger RNA
  • Nuclear Proteins
  • Odds Ratio
  • Population
  • Proteins
  • Systemic Lupus Erythematosus
  • Ubiquitin

International Standard Serial Number (ISSN)

  • 1061-4036

number of pages

  • 6

start page

  • 253

end page

  • 8