Association of TNFSF15 polymorphism with irritable bowel syndrome

Marco Zucchelli, Michael Camilleri, Anna Nixon Andreasson, Francesca Bresso, Aldona Dlugosz, Jonas Halfvarson, Leif Torkvist, Peter T. Schmidt, Pontus Karling, Bodil Ohlsson, Richard H. Duerr, Magnus Simren, Greger Lindberg, Lars Agreus, Paula Carlson, Alan R. Zinsmeister, Mauro D'Amato

    Research output: Contribution to journalArticlepeer-review

    97 Citations (SciVal)

    Abstract

    Background Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder, affecting more than 10% of the general population worldwide. Although a genetic component is suspected, unambiguous susceptibility genes have so far not been identified. This study tested the hypothesis that genes contributing to epithelial barrier integrity, control of mucosal immune responses and interactions with bacteria in the gut are associated with IBS. Methods Single nucleotide polymorphisms (SNPs) corresponding to top signals of association with Crohn's disease at 30 known susceptibility loci were tested for their effect on IBS risk in 1992 individuals from two independent case-control cohorts from Sweden and the USA. Association tests included a conservative Bonferroni correction for multiple comparisons, and were also performed on specific subgroups of patients characterised by constipation (IBS-C), diarrhoea (IBS-D) or alternating constipation and diarrhoea (IBS-A). Results The Crohn's disease risk allele rs4263839 G in the TNFSF15 gene was significantly associated with an increased risk of both IBS (p=2.2 x 10(-5); OR 1.37) and more pronouncedly, IBS-C (p=8.7 x 10(-7); OR 1.79) in the entire sample. Similar associations and risk effects of the same magnitude were observed in the two cohorts analysed separately. A correlation between rs4263839 genotype and TNFSF15 mRNA expression was detected both in peripheral blood and in rectal mucosal biopsies from healthy individuals (combined p=0.0033). Conclusions TNFSF15 is a susceptibility gene for IBS and IBS constipation. As TL1A, the protein encoded by TNFSF15, contributes to the modulation of inflammatory responses, the results support a role of immune activation in IBS.
    Original languageEnglish
    Pages (from-to)1671-1677
    JournalGut
    Volume60
    Issue number12
    DOIs
    Publication statusPublished - 2011

    Subject classification (UKÄ)

    • Gastroenterology and Hepatology

    Fingerprint

    Dive into the research topics of 'Association of TNFSF15 polymorphism with irritable bowel syndrome'. Together they form a unique fingerprint.

    Cite this