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

Dideberg, Vinciane; Kristjansdottir, G.; Milani, L.; Libioulle, Cécile; Sigurdsson, S.; Louis, Edouard; Wiman, A. C.; Vermeire, S.; Rutgeerts, P.; Belaiche, Jacques; Franchimont, D.; Van Gossum, A.; Bours, Vincent; Syvanen, A. C.

doi:10.1093/hmg/ddm259

Article (Scientific journals)

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

Dideberg, Vinciane; Kristjansdottir, G.; Milani, L. et al.

2007 • In Human Molecular Genetics, 16 (24), p. 3008-3016

Peer Reviewed verified by ORBi

Permalink
https://hdl.handle.net/2268/26560

DOI
10.1093/hmg/ddm259

PubMed
17881657

Files (1)Send to Details Statistics Bibliography Similar publications

Files

Full Text

Hum Mol Genet 2007 16 3008-16.pdf

Publisher postprint (411.23 kB)

Download

All documents in ORBi are protected by a user license.

Send to

RIS BibTex APA Chicago Permalink X Linkedin

Details

Abstract :

[en] 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=1.9x10(-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=6.8x10(-4)) and was particularly strong among the UC patients [P=5.3x10(-8), OR=2.42 (1.76-3.34)]. The association of the CGGGG indel was confirmed in the second cohort [P=3.2x10(-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.

Disciplines :

Biochemistry, biophysics & molecular biology
Genetics & genetic processes

Author, co-author :

Dideberg, Vinciane ; Centre Hospitalier Universitaire de Liège - CHU > Génétique

Kristjansdottir, G.

Milani, L.

Libioulle, Cécile ; Université de Liège - ULiège > Génétique

Sigurdsson, S.

Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie

Wiman, A. C.

Vermeire, S.

Rutgeerts, P.

Belaiche, Jacques ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie

More authors (4 more)

Language :

English

Title :

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

Publication date :

15 December 2007

Journal title :

Human Molecular Genetics

ISSN :

0964-6906

eISSN :

1460-2083

Publisher :

Oxford Univ Press, Oxford, United Kingdom

Volume :

Issue :

Pages :

3008-3016

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 26 October 2009

Statistics

Number of views

262 (1 by ULiège)

Number of downloads

289 (1 by ULiège)

More statistics

Scopus citations^®

160

Scopus citations^®
without self-citations

151

OpenCitations

135

OpenAlex citations

182

Bibliography

Danese, S., Sans, M. and Fiocchi, C. (2004) Inflammatory bowel disease: the role of environmental factors. Autoimmun. Rev., 3, 394-400.
Kuster, W., Pascoe, L., Purrmann, J., Funk, S. and Majewski, F. (1989) The genetics of Crohn disease: Complex segregation analysis of a family study with 265 patients with Crohn disease and 5,387 relatives. Am. J. Med. Genet., 32, 105-108.
Orholm, M., Binder, V., Sorensen, T.I., Rasmussen, L.P. and Kyvik, K.O. (2000) Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study. Scand. J. Gastroenterol., 35, 1075-1081.
Russell, R.K., Wilson, D.C. and Satsangi, J. (2004) Unravelling the complex genetics of inflammatory bowel disease. Arch. Dis. Child., 89, 598-603.
Thompson, U.P., Driscoll, R., Pounder, R.E. and Wakefield, A.J. (1996) Genetics versus environment in inflammatory bowel disease: Results of a British twin study. BMJ, 312, 95-96.
Lesage, S., Zouali, H., Cezard, J.P., Colombel, J.F., Belaiche, J., Almer, S., Tysk, C., O'Morain, C., Gassull, M., Binder, V. et al. (2002) CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am. J. Hum. Genet., 70, 845-857.
Hampe, J., Franke, A., Rosenstiel, P., Till, A., Teuber, M., Huse, K., Albrecht, M., Mayr, G., De La Vega, F.M., Briggs, J. et al. (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat. Genet., 39, 207-211.
Duerr, R.H., Taylor, K.D., Brant, S.R., Rioux, J.D., Silverberg, M.S., Daly, M.J., Steinhart, A.H., Abraham, C., Regueiro, M., Griffiths, A. et al. (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene Novel susceptibility genes in inflammatory bowel disease. Science, 314, 1461-1463.
Libioulle, C., Louis, E., Hansoul, S., Sandor, C., Farnir, F., Franchimont, D., Vermeire, S., Dewit, O., de Vos, M., Dixon, A. et al. (2007) Novel Crohn Disease Locus Identified by Genome-Wide Association Maps to a Gene Desert on 5p13.1 and Modulates Expression of PTGER4. PLoS Genet., 3, e58.
Wellcome Trust Case Control Consortium. (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447, 661-678.
Parkes, M., Barrett, J.C., Prescott, N.J., Tremelling, M., Anderson, C.A., Fisher, S.A., Roberts, R.G., Nimmo, E.R., Cummings, F.R., Soars, D. et al. (2007) Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat. Genet., 39, 830-832.
Becker, K.G., Simon, R.M., Bailey-Wilson, J.E., Freidlin, B., Biddison, W.E., McFarland, H.F. and Trent, J.M. (1998) Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases. Proc. Natl Acad. Sci. USA, 95, 9979-9984.
Weng, X., Liu, L., Barcellos, L.F., Allison, J.E. and Herrinton, L.J. (2007) Clustering of Inflammatory Bowel Disease With Immune Mediated Diseases Among Members of a Northern California-Managed. Care Organization. Am. J. Gastroenterol., 102, 1429-1435.
Shiina, T., Inoko, H. and Kulski, J.K. (2004) An update of the HLA genomic region, locus information and disease associations: 2004. Tissue Antigens, 64, 631-649.
Lee, Y.H., Rho, Y.H., Choi, S.J., Ji, J.D., Song, G.G., Nath, S.K. and Harley, J.B. (2007) The PTPN22 C1858T functional polymorphism and autounimine diseases - a meta-analysis. Rheumatology, 46, 49-56.
Kavvoura, F.K., Akamizu, T., Awata, T., Ban, Y., Chistiakov, D.A., Frydecka, I., Ghaderi, A., Gough, S.C., Hiromatsu, Y., Ploski, R. et al. (2007) CTLA-4 gene polymorphisms and autoimmune thyroid disease: a meta anilysis. J. Clin. Endocrinol. Metab., 92, 3162-3170.
Wen, Z. and Fiocchi, C. (2004) Inflammatory bowel disease: Autoimmune or immune-mediated pathogenesis? Clin. Dev. Immunol., 11, 195-204.
Marie, I., Durbin, J.E. and Levy, D.E. (1998) Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. EMBO J., 17, 6660-6669.
Lin, R., Heylbroeck, C., Pitha, P.M. and Hiscott, J. (1998) Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation. Mol. Cell. Biol., 18, 2986-2996.
Zhang, L., Wu, L., Hong, K. and Pagano, J.S. (2001) Intracellular signaling molecules activated by Epstein-Barr virus for induction of interferon regulatory factor 7. J. Virol., 75, 12393-12401.
Cheng, T.-F., Brzostek, S., Ando, O., Van Scoy, S., Kumar, K.P. and Reich, N.C. (2006) Differential activation of IFN Regulatory Fact of (IRF)-3 and IRF-5 transcription factors during viral infection. J. Immunol., 176, 7462-7470.
Honda, K. and Taniguchi, T. (2006) IRFs: Master regulars of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat. Rev. Immunol., 6, 644-658.
Barnes, B.J., Field, A.E. and Pitha-Rowe, P.M. (2003) Virus-induced heterodimer formation between IRF-5 and IRF-7 modulates assembly of the IFNA enhanceosome in vivo and transcriptional activity of IFNA genes. J Biol. Chem., 278, 16630-16641.
Takaoka, A., Yanai, H., Kondo, S., Duncan, G., Negishi, H., Mizutani, T. Kano, S.-I., Honda, K., Ohba, Y., Mak, T.W. et al. (2005) Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature, 434, 243-249.
O'Neill, L.A.J. and Bowie, A.G. (2007) The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol., 7, 353-364.
Ouyang, X., Negishi, H., Takeda, R., Fujita, Y., Taniguchi, T. and Honda, K. (2007) Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5par activation. Biochem. Biophys. Res. Commun., 354, 1045-1051.
Nakamura, K., Honda, K., Mizutani, T., Akiho, H. and Harada, N. (2006) Novel strategies for the treatment of inflammatory bowel disease: selective inhibition of cytokines and adhesion molecules. World J. Gastroenterol., 12, 4628-4635.
Sigurdsson, S., Nordmark, G., Goring, H.H., Lindroos, K., Wiman, A.C., Sturfelt, G., Jonsen, X., Rantapaa-Dahlqvist, S., Moller, B., Kere, J. et al. (2005) Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic hipus erythematosus. Am. J. Hum. Genet., 76, 528-537.
Graham, R.R., Kozyrev, S.V., Baechler, E.C., Reddy, M.V., Plenge, R.M., Bauer, J.W., Ortmann, W.A., Koeuth, T., Escribano, M.F. Argentine and Collaborative Groups et al. (2006) A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat. Genet., 38, 550-555.
Sigurdsson, S., Padyukov, L., Kurreeman, F., Liljedahl, U., Wiman, A.C., Alfredsson, L., Toes, R., Rönnelid, J., Klareskog, L., Huizinga, T. et al. (2007) Association of a haplotype in the promoter region of the interferon regulatory factor 5 gene with rheumatoid arthritis. Arthritis Rheum., 56, 2202-2210.
Heinemeyer, T., Wingender, E., Reuter, I., Hermjakob, H., Kel, A.E., Kel, O.V., Ignatieva, E.V., Ananko, E.A., Podkolodnaya, O.A., Kolpakov, F.A. et al. (1998) Databases on Transcriptional Regulation: TRANSFAC, TRRD, and COMPEL. Nucleic Acids Res., 26, 364-370.
Graham, R.R., Kyogoku, C., Sigurdsson, S., Vlasova, I.A., Davies, L.R., Baechler, E.C., Plenge, R.M., Koeuth, T., Ortmann, W.A., Hom, G. et al. (2007) Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proc. Natl Acad. Sci. USA, 104, 6758-6763.
Bergman, L., Lindblom, J.B., Safwenberg, J. and Krause, U. (1976) HL-A frequencies in Crohn's disease and ulcerative colitis. Tissue Antigens, 7, 145-150.
Gaya, D.R., Russell, R.K., Nimmo, E.R. and Satsangi, J. (2006) New genes in inflammatory bowel disease: Lessons for complex diseases? Lancet 367, 1271-1284.
Cho, J.H., Nicolae, D.L., Gold, L.H., Fields, C.T.,LaBuda, M.C., Rohal, P.M., Pickles, M.R., Qin. L., Fu, Y., Mann, I. S. et al. (1998) Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1. PNAS, 95, 7502-7507.
Hampe, J., Shaw, S.H., Saiz, R., Leysens, N., Lantermannn, A., Mascheretti, S., Lynch, N.J., MacPherson, A.J.;Bridger, S., van Deventer, S. et al. (1999) Linkage of inflammatory bowel disease to human chromosome 6p. Am. J. Hum. Genet., 65, 1647-1653.
Cummings, J.R., Cooney, R., Pathan, S., Anderson, C., Barrett, J., Beckly, J., Geremia, A., Hancock, L., Guo, C., Ahmad, T. et al. (2007) Confirmation of the role of ATG1611 as a Crohn's disease susceptibility gene. Inflamm. Bowel Dis., 13, 941-946.
Tremelling, M., Cummings, F., Fisher, S.A., Mansfield; J., Gwilliam, R., Keniry,. A., Nimmo, E.R., Drummond, H., Onnie, C.M., Prescott, N.J. et al. (2007) IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology, 132, 1657-1664.
De Jager, P.L., Graham, R., Farwell, L., Sawcer, S., Richardson, A., Behrens, T.W., Compston, A., Hafler, D.A., Kere, J., Vyse, T.J. et al. (2006) The role of inflammatory bowel disease susceptibility loci in multiple sclerosis and systemic lupus erythematosus. Genes Immun. 7, 327-334.
Ferreiros-Vidal, I., Garcia-Meijide, J., Carreira, P., Barros, F., Carracedo, A., Gomez-Reino, J.J. and Gonzalez, A. (2003) The three most common CARD15 mutations associated with Crohn's disease and the chromosome 16 susceptibility locus for systemic lupus erythematosus. Rheumatology, 42, 570-574.
Chong, W.P., Ip, W.K., Lau, C.S., Chan, T.M., Padyukov, L. and Lau, Y.L. (2004) Common NOD2 polymorphisms in Hong Kong Chinese patients with systemic lupus erythematosus. Rheumatology, 43, 104-105.
Ferreiro-Neira, I., Calaza, M., Alonso-Perez, E., Marchini, M., Scorza, R., Sebastiani, G.D., Blanco, F.J., Rego, I., Pullmann, R., Pullmann, R. et al. (2007) Opposed independent effects and epistasis in the complex association of IRF5 to SLE. Genes Immun., 8, 429-438.
Sharma, S., Grandvaux, N., Mamane, Y., Genin, P., Azimi, N., Waldmann, T. and Hiscott, J. (2002) Regulation of IFN Regulatory Factor 4 Expression in Human T Cell Leukemia Virus-I-Transformed T Cells. J. Immunol., 169, 3120-3130.
McAlexander, M.B. and Yu-Lee, L.-Y. (2001) Spl is required for prolactin activation of the interferon regulatory factor-1 gene. Mol. Cell. Endocrinol., 184, 135-141.
Bell, P.A., Chaturvedi, S., Gelfand, C.A, Huang, C.Y., Kochersperger, M., Kopla, R., Modica, F., Pohl, M., Varde, S., Zhao, R. et al. (2002) SNPstream UHT: Ultra-high throughput SNP genotyping for pharmacogenomics and drug discovery. Biotechniques, 32 (Suppl.), 70-72, 74, 76-77.
Hsu, T.M., Chen, X., Duan, S., Miller, R.D. and Kwok, P.Y. (2001) Universal SNP genotyping assay with fluorescence polarization detection. Biotechniques, 31, 560-562, 564-568.
Barrett, J.C., Fry, B., Maller, J. and Daly, M.J. (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263-265.
Scheet, P. and Stephens, M. (2006) A fast and flexible statistical model for large-scale population genotype data: Applications to inferring missing genotypes and haplotypic phase. Am. J. Hum. Genet., 78 629-644.
Graham, D.S.C., Manku, H., Wagner, S., Reid, J., Timms, K., Gutin, A., Lanchbury, J.S. and Vyse, T.J. (2007) Association of IRF5 in UK SLE families identifies a variant involved in polyadenylation. Hum. Mol. Genet., 16, 579-591.
Cheung, V.G., Spielman, R.S., Ewens, K.G., Weber, T.M., Morley, M. and Burdick. J.T. (2005) Mapping determinants of human gene expression by regional and genome-wide association. Nature, 437, 1365-1369.