Host genetics and IBS

Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder but its aetiology remains poorly understood. A genetic link in IBS is supported by familial clustering and a higher incidence in monozygotic twins. In this issue of Gut, Zucchelli et al examined 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. They tested 30 known susceptibility loci for Crohn's disease in 1992 individuals from two independent case-control cohorts from Sweden and the USA. The Crohn's disease risk allele rs4263839 G in the TNFSF15 gene was significantly associated with an increased risk of both IBS (p=2.2310⁻⁵; OR 1.37) and more markedly, constipation predominant IBS (p=8.7310⁻⁷; OR 1.79). Furthermore, the polymorphism was shown to be functional with the G allele correlating with higher TNFSF15 mRNA expression in blood and rectal mucosal of healthy individuals (see figure 1). This gene is involved in the regulation of immune and inflammatory responses supporting a role for these pathways in the pathogenesis of IBS. The findings of this study might ultimately lead to …