An insertion-deletion polymorphism in the Interferon Regulatory Factor 5 (IRF5) gene confers risk of inflammatory bowel diseases

The interferon regulatory factor 5 (IRF5) gene encodes a transcriptionfactor that plays an important role in the innate as well asin the cell-mediated immune responses. The IRF5 gene has beenshown to be associated with systemic lupus erythematosus andrheumatoid arthritis. We studied whether the IRF5 gene is alsoassociated with inflammatory bowel diseases (IBD), Crohn disease(CD) and ulcerative colitis (UC). Twelve polymorphisms in theIRF5 gene were genotyped in a cohort of 1007 IBD patients (748CD and 241 UC) and 241 controls from Wallonia, Belgium. Thesame polymorphisms were genotyped in a confirmatory cohort of311 controls and 687 IBD patients (488 CD and 192 UC) from Leuven,Belgium. A strong signal of association (p = 1.9 x 10–5,OR: 1.81 (1.37-2.39)) with IBD was observed for a 5bp indel(CGGGG) polymorphism in the promoter region of the IRF5 gene.The association was detectable (p = 6.8 x 10–4) also inCD patients, and was particularly strong among the UC patients(p = 5.3 x 10–8, OR 2.42 (1.76 -3.34)). The associationof the CGGGG indel was confirmed in the second cohort (p = 3.2x 10–5, OR 1.59 (1.28 - 1.98)). The insertion of one CGGGGunit is predicted to create an additional binding site for thetranscription factor SP1. Using an electrophoretic mobilityshift assay we show allele-specific differences in protein bindingto this repetitive DNA-stretch, which suggest a potential functionrole for the CGGGG indel.

Kristjansdottir, GudlaugUppsala universitet,Molekylär medicin (author)
Milani, LiliUppsala universitet,Molekylär medicin(Swepub:uu)livoj956 (author)
Libioulle, C. (author)
Sigurdsson, SnaevarUppsala universitet,Molekylär medicin (author)
Louis, E. (author)
Wiman, Ann-ChristinUppsala universitet,Molekylär medicin (author)
Vermeire, S. (author)
Rutgeerts, P. (author)
Belaiche, J. (author)
Franchimont, D. (author)
Van Gossum, A. (author)
Bours, V. (author)
Syvänen, Ann-ChristineUppsala universitet,Molekylär medicin(Swepub:uu)anncsyva (author)
Uppsala universitetMolekylär medicin (creator_code:org_t)

In:Human Molecular Genetics: Oxford University Press (OUP)16:24, s. 3008-30160964-69061460-2083

By the author/editor: Dideberg, Vincia ...; Kristjansdottir, ...; Milani, Lili; Libioulle, C.; Sigurdsson, Snae ...; Louis, E.; show more...; Wiman, Ann-Chris ...; Vermeire, S.; Rutgeerts, P.; Belaiche, J.; Franchimont, D.; Van Gossum, A.; Bours, V.; Syvänen, Ann-Chr ...; show less...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.