Identifying and testing candidate genetic polymorphisms in irritable bowel syndrome: association with TNFSF15 and tumor necrosis factor-α

Although irritable bowel syndrome (IBS) is extremely common, few studies have examined the interaction between environmental factors and genetic polymorphisms in IBS. Over the last decade, increasing evidence suggests that genetic factors contribute to the development of IBS. In a recent study published in Gut, Swan et al identified genetic polymorphisms, which may be associated with IBS [1]. Swan hypothesized that genetic markers whose expression was altered by Campylobacter jejuni (C. jejuni) gastroenteritis may be linked to IBS with diarrhea (IBS-D), which closely resembles post-infectious IBS (PI-IBS) [1]. Swan’s hypothesis was that patients with IBS-D have a genetic tendency to overreact to inflammatory insults and show immune activation. In a two-part study, healthy patients, patients 6 months after C. jejuni infection, and patients with IBS-D and IBS with constipation (IBS-C) underwent rectal biopsies for gene expression analysis and peripheral blood cell cytokine (inflammatory marker) assessment. Polymorphisms in gene expression that were altered by C. jejuni gastroenteritis were similar to mucosal gene expression seen in IBS-D. Part one of the study assessed gene expression in the rectal mucosa both 6 months after C. jejuni infection and in chronic IBS patients compared with healthy volunteers. The authors showed that mucosal expression of seven genes was altered in IBS, and that these alterations in mucosal expression were similar to those seen in PI-IBS after C. jejuni infection. Part two of the study assessed 21 known single-nucleotide genetic polymorphisms