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The interferon regulatory factor 5 (IRF5) gene encodes a transcription factor that plays an important role in the innate as well as in the cell-mediated immune responses. The IRF5 gene has been shown to be associated with systemic lupus erythematosus and rheumatoid arthritis. We studied whether the IRF5 gene is also associated with inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). Twelve polymorphisms in the IRF5 gene were genotyped in a cohort of 1007 IBD patients (748 CD and 254 UC) and 241 controls from Wallonia, Belgium. The same polymorphisms were genotyped in a confirmatory cohort of 311 controls and 687 IBD patients (488 CD and 192 UC) from Leuven, Belgium. A strong signal of association [ P =1.9×10 −5 , odds ratio (OR) 1.81 (1.37–2.39)] with IBD was observed for a 5 bp indel (CGGGG) polymorphism in the promoter region of the IRF5 gene. The association was detectable also in CD patients ( P =6.8×10 −4 ) and was particularly strong among the UC patients [ P =5.3×10 −8 , OR=2.42 (1.76–3.34)]. The association of the CGGGG indel was confirmed in the second cohort [ P =3.2×10 −5 , OR=1.59 (1.28–1.98)]. The insertion of one CGGGG unit is predicted to create an additional binding site for the transcription factor SP1. Using an electrophoretic mobility shift assay, we show allele-specific differences in protein binding to this repetitive DNA-stretch, which suggest a potential function role for the CGGGG indel.

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