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TNFSF15 polymorphisms are associated with susceptibility to inflammatory bowel disease in a new European cohort
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2009 (English)In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 104, no 2, p. 384-391Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Inflammatory bowel disease (IBD), e.g., Crohn's disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD. METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied. RESULTS: The previously reported "high-risk" haplotype (A) was associated with IBD (P=0.001) (OR=1.25 (1.05-1.50)) and CD (P=0.02) (OR=1.31 (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A. CONCLUSIONS: This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.

Place, publisher, year, edition, pages
2009. Vol. 104, no 2, p. 384-391
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Research subject
Medicine
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URN: urn:nbn:se:oru:diva-12128DOI: 10.1038/ajg.2008.36ISI: 000263566300020PubMedID: 19174806Scopus ID: 2-s2.0-59749094752OAI: oai:DiVA.org:oru-12128DiVA, id: diva2:355661
Available from: 2010-10-07 Created: 2010-10-07 Last updated: 2017-12-12Bibliographically approved

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Tysk, Curt

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