Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-03

AUTHORS

Indra Adrianto, Feng Wen, Amanda Templeton, Graham Wiley, Jarrod B King, Christopher J Lessard, Jared S Bates, Yanqing Hu, Jennifer A Kelly, Kenneth M Kaufman, Joel M Guthridge, Marta E Alarcón-Riquelme, Juan-Manuel Anaya, Sang-Cheol Bae, So-Young Bang, Susan A Boackle, Elizabeth E Brown, Michelle A Petri, Caroline Gallant, Rosalind Ramsey-Goldman, John D Reveille, Luis M Vila, Lindsey A Criswell, Jeffrey C Edberg, Barry I Freedman, Peter K Gregersen, Gary S Gilkeson, Chaim O Jacob, Judith A James, Diane L Kamen, Robert P Kimberly, Javier Martin, Joan T Merrill, Timothy B Niewold, So-Yeon Park, Bernardo A Pons-Estel, R Hal Scofield, Anne M Stevens, Betty P Tsao, Timothy J Vyse, Carl D Langefeld, John B Harley, Kathy L Moser, Carol F Webb, Mary Beth Humphrey, Courtney Gray Montgomery, Patrick M Gaffney

ABSTRACT

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. More... »

PAGES

253

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.766

    DOI

    http://dx.doi.org/10.1038/ng.766

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1032897455

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21336280


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