Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility - PubMed (original) (raw)
. 2008 Nov;40(11):1319-23.
doi: 10.1038/ng.221. Epub 2008 Oct 5.
Tobias Balschun, Tom H Karlsen, Jurgita Sventoraityte, Susanna Nikolaus, Gabriele Mayr, Francisco S Domingues, Mario Albrecht, Michael Nothnagel, David Ellinghaus, Christian Sina, Clive M Onnie, Rinse K Weersma, Pieter C F Stokkers, Cisca Wijmenga, Maria Gazouli, David Strachan, Wendy L McArdle, Séverine Vermeire, Paul Rutgeerts, Philip Rosenstiel, Michael Krawczak, Morten H Vatn; IBSEN study group; Christopher G Mathew, Stefan Schreiber
Collaborators, Affiliations
- PMID: 18836448
- DOI: 10.1038/ng.221
Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility
Andre Franke et al. Nat Genet. 2008 Nov.
Abstract
Inflammatory bowel disease (IBD) typically manifests as either ulcerative colitis (UC) or Crohn's disease (CD). Systematic identification of susceptibility genes for IBD has thus far focused mainly on CD, and little is known about the genetic architecture of UC. Here we report a genome-wide association study with 440,794 SNPs genotyped in 1,167 individuals with UC and 777 healthy controls. Twenty of the most significantly associated SNPs were tested for replication in three independent European case-control panels comprising a total of 1,855 individuals with UC and 3,091 controls. Among the four consistently replicated markers, SNP rs3024505 immediately flanking the IL10 (interleukin 10) gene on chromosome 1q32.1 showed the most significant association in the combined verification samples (P = 1.35 x 10(-12); OR = 1.46 (1.31-1.62)). The other markers were located in ARPC2 and in the HLA-BTNL2 region. Association between rs3024505 and CD (1,848 cases, 1,804 controls) was weak (P = 0.013; OR = 1.17 (1.01-1.34)). IL10 is an immunosuppressive cytokine that has long been proposed to influence IBD pathophysiology. Our findings strongly suggest that defective IL10 function is central to the pathogenesis of the UC subtype of IBD.
Similar articles
- The Polymorphism rs3024505 (C/T) Downstream of the IL10 Gene Is Associated with Crohn's Disease in Serbian Patients with Inflammatory Bowel Disease.
Mijac D, Petrovic IV, Djuranovic S, Perovic V, Bojic D, Culafic D, Popovic D, Krstic M, Jankovic G, Djoric M, Pravica V, Markovic M. Mijac D, et al. Tohoku J Exp Med. 2016 Sep;240(1):15-24. doi: 10.1620/tjem.240.15. Tohoku J Exp Med. 2016. PMID: 27558476 - Genetic susceptibility in IBD: overlap between ulcerative colitis and Crohn's disease.
Doecke JD, Simms LA, Zhao ZZ, Huang N, Hanigan K, Krishnaprasad K, Roberts RL, Andrews JM, Mahy G, Bampton P, Lewindon P, Florin T, Lawrance IC, Gearry RB, Montgomery GW, Radford-Smith GL. Doecke JD, et al. Inflamm Bowel Dis. 2013 Feb;19(2):240-5. doi: 10.1097/MIB.0b013e3182810041. Inflamm Bowel Dis. 2013. PMID: 23348120 - An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians.
Juyal G, Prasad P, Senapati S, Midha V, Sood A, Amre D, Juyal RC, BK T. Juyal G, et al. PLoS One. 2011 Jan 31;6(1):e16565. doi: 10.1371/journal.pone.0016565. PLoS One. 2011. PMID: 21304977 Free PMC article. - The genetics of Crohn's disease and ulcerative colitis--status quo and beyond.
Ellinghaus D, Bethune J, Petersen BS, Franke A. Ellinghaus D, et al. Scand J Gastroenterol. 2015 Jan;50(1):13-23. doi: 10.3109/00365521.2014.990507. Scand J Gastroenterol. 2015. PMID: 25523552 Review. - Genetics of ulcerative colitis.
Thompson AI, Lees CW. Thompson AI, et al. Inflamm Bowel Dis. 2011 Mar;17(3):831-48. doi: 10.1002/ibd.21375. Epub 2010 Nov 12. Inflamm Bowel Dis. 2011. PMID: 21319274 Review.
Cited by
- Systematic perturbation screens identify regulators of inflammatory macrophage states and a role for TNF mRNA m6A modification.
Haag SM, Xie S, Eidenschenk C, Fortin JP, Callow M, Costa M, Lun A, Cox C, Wu SZ, Pradhan RN, Lock J, Kuhn JA, Holokai L, Thai M, Freund E, Nissenbaum A, Keir M, Bohlen CJ, Martin S, Geiger-Schuller K, Hejase HA, Yaspan BL, Melo Carlos S, Turley SJ, Murthy A. Haag SM, et al. Nat Genet. 2024 Nov;56(11):2493-2505. doi: 10.1038/s41588-024-01962-w. Epub 2024 Oct 23. Nat Genet. 2024. PMID: 39443811 - Effects of breast-fed infants-derived Limosilactobacillus reuteri and Bifidobacterium breve ameliorate DSS-induced colitis in mice.
Huang Z, Liu B, Xiao L, Liao M, Huang L, Zhao X, Ma K, Wang R, Ji F, Li W, Huang L, Xie L. Huang Z, et al. iScience. 2024 Sep 11;27(10):110902. doi: 10.1016/j.isci.2024.110902. eCollection 2024 Oct 18. iScience. 2024. PMID: 39351200 Free PMC article. - Autoimmunity-Associated SNP rs3024505 Disrupts STAT3 Binding in B Cells, Leading to IL10 Dysregulation.
Uvarova AN, Zheremyan EA, Ustiugova AS, Murashko MM, Bogomolova EA, Demin DE, Stasevich EM, Kuprash DV, Korneev KV. Uvarova AN, et al. Int J Mol Sci. 2024 Sep 23;25(18):10196. doi: 10.3390/ijms251810196. Int J Mol Sci. 2024. PMID: 39337678 Free PMC article. - Evaluating the causal effect of circulating proteome on the risk of inflammatory bowel disease-related traits using Mendelian randomization.
Li B, Hu P, Liang H, Zhao X, Zhang A, Xu Y, Zhang B, Zhang J. Li B, et al. Front Immunol. 2024 Jul 31;15:1434369. doi: 10.3389/fimmu.2024.1434369. eCollection 2024. Front Immunol. 2024. PMID: 39144148 Free PMC article. - IL-10 Counteracts IFN-γ to Alleviate Acute Lung Injury in a Viral-Bacterial Superinfection Model.
McKelvey M, Uddin MB, Palani S, Shao S, Sun K. McKelvey M, et al. Am J Respir Cell Mol Biol. 2024 Jul;71(1):110-120. doi: 10.1165/rcmb.2023-0437OC. Am J Respir Cell Mol Biol. 2024. PMID: 38574279
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous