| Tumour necrosis factor-alpha receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab. | |
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MedLine Citation:
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PMID: 15274667 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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M Pierik; S Vermeire; K V Steen; S Joossens; G Claessens; R Vlietinck; P Rutgeerts |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Alimentary pharmacology & therapeutics Volume: 20 ISSN: 0269-2813 ISO Abbreviation: Aliment. Pharmacol. Ther. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-07-27 Completed Date: 2004-12-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8707234 Medline TA: Aliment Pharmacol Ther Country: England |
Other Details:
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Languages: eng Pagination: 303-10 Citation Subset: IM |
Affiliation:
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Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Aged, 80 and over Antibodies, Monoclonal / therapeutic use* C-Reactive Protein / analysis Colitis, Ulcerative / drug therapy, genetics* Crohn Disease / drug therapy, genetics* Female Follow-Up Studies Gastrointestinal Agents / therapeutic use* Genotype Humans Male Middle Aged Mutation / genetics Polymorphism, Genetic / genetics Prospective Studies Receptors, Tumor Necrosis Factor / genetics Receptors, Tumor Necrosis Factor, Type I / genetics* Receptors, Tumor Necrosis Factor, Type II / genetics* Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Gastrointestinal Agents; 0/Receptors, Tumor Necrosis Factor; 0/Receptors, Tumor Necrosis Factor, Type I; 0/Receptors, Tumor Necrosis Factor, Type II; 0/infliximab; 9007-41-4/C-Reactive Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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