PT  - JOURNAL ARTICLE
AU  - Marco Zucchelli
AU  - Michael Camilleri
AU  - Anna Nixon Andreasson
AU  - Francesca Bresso
AU  - Aldona Dlugosz
AU  - Jonas Halfvarson
AU  - Leif Törkvist
AU  - Peter T Schmidt
AU  - Pontus Karling
AU  - Bodil Ohlsson
AU  - Richard H Duerr
AU  - Magnus Simren
AU  - Greger Lindberg
AU  - Lars Agreus
AU  - Paula Carlson
AU  - Alan R Zinsmeister
AU  - Mauro D'Amato
TI  - Association of <em>TNFSF15</em> polymorphism with irritable bowel syndrome
AID  - 10.1136/gut.2011.241877
DP  - 2011 Dec 01
TA  - Gut
PG  - 1671--1677
VI  - 60
IP  - 12
4099  - http://gut.bmj.com/content/60/12/1671.short
4100  - http://gut.bmj.com/content/60/12/1671.full
SO  - Gut2011 Dec 01; 60
AB  - 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=2.2×10−5; OR 1.37) and more pronouncedly, IBS-C (p=8.7×10−7; 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.