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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/2203

Title: Tumour necrosis factor-alpha receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab
Authors: Pierik, M
Vermeire, S
VAN STEEN, Kristel
Joossens, S
Claessens, G
Vlietinck, R
Rutgeerts, P
Issue Date: 2004
Publisher: BLACKWELL PUBLISHING LTD
Citation: ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 20(3). p. 303-310
Abstract: Background: The role of tumour necrosis factor-alpha in the pathogenesis of inflammatory bowel disorders is well-known and is underscored by the effectiveness of antitumour necrosis factor-alpha treatment. Tumour necrosis factor-alpha exerts its effect by binding TNFR1 and TNFR2, which genes map to inflammatory bowel disorders susceptibility loci. Aims and methods: Since TNFR1 and TNFR2 are good candidate genes for inflammatory bowel disorders, we studied the functional TNFR2T587G and the TNFR1A36G mutation in 344 Crohn's disease and 152 ulcerative colitis patients and investigated the relation with disease phenotypes. An association with response to infliximab was evaluated in 166 Crohn's disease patients. Results: The TNFR2 587G allele was more frequent in ulcerative colitis compared with controls (P = 0.03). Both single nucleotide polymorphisms were negatively associated with smoking at diagnosis in Crohn's disease (TNFR1A36G odds ratio: 0.614, 95% confidence interval: 0.452, 0.99 and TNFR2T587G odds ratio: 0.572, 95% confidence interval: 0.820, 0.875). There was a positive association between pancolitis and the TNFR1A36G polymorphism in ulcerative colitis (odds ratio: 5.341, 95% confidence interval: 1.484, 19.39). The biological response to infliximab was lower in patients carrying TNFR1 36G (odds ratio: 0.47, 95% confidence interval: 0.234, 0.946). Conclusion: The TNFR2 587G allele was more frequent in ulcerative colitis. Both single nucleotide polymorphisms were negatively associated with smoking in Crohn's disease. A relation between TNFR1A36G and pancolitis was found in ulcerative colitis. There was no clear effect of the polymorphisms on infliximab response although, the TNFR1 minor was associated with a lower response to infliximab.
Notes: Univ Hosp Gasthuisberg, Dept Gastroenterol, B-3000 Louvain, Belgium. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Limburgs Univ Ctr, Ctr Stat, Diepenbeek, Belgium. Katholieke Univ Leuven, Ctr Epidemiol & Human Genet, Louvain, Belgium.Rutgeerts, P, Univ Hosp Gasthuisberg, Dept Gastroenterol, Herestr 49, B-3000 Louvain, Belgium.paul.rutgeerts@uz.kuleuven.ac.be
URI: http://hdl.handle.net/1942/2203
DOI: 10.1111/j.1365-2036.2004.01946.x
ISI #: 000222945100007
ISSN: 0269-2813
Category: A1
Type: Journal Contribution
Validation: ecoom, 2005
Appears in Collections: Research publications

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