Genetic Association Analysis of the Functional c.714T.G Polymorphism and Mucosal Expression of Dectin-1 in Inflammatory Bowel Disease

Background: Dectin-1 is a pattern recognition receptor (PRR) expressed by myeloid cells that specifically recognizes b-1,3 glucan, a polysaccharide and major component of the fungal cell wall. Upon activation, dectin-1 signaling converges, similar to NOD2, on the adaptor molecule CARD9 which is associated with inflammatory bowel disease (IBD). An early stop codon polymorphism (c.714T.G) in DECTIN-1 results in a loss-of-function (p.Y238X) and impaired cytokine responses, including TNF-a, interleukin (IL)-1b and IL-17 upon in vitro stimulation with Candida albicans or b-glucan. The aim of the present study was to test the hypothesis that the DECTIN-1 c.714T.G (p.Y238X) polymorphism is associated with lower disease susceptibility or severity in IBD and to investigate the level of dectin-1 expression in inflamed and non-inflamed colon tissue of IBD patients. Methodology: Paraffin embedded tissue samples from non-inflamed and inflamed colon of IBD patients and from diverticulitis patients were immunohistochemically stained for dectin-1 and related to CD68 macrophage staining. Genomic DNA of IBD patients (778 patients with Crohn’s disease and 759 patients with ulcerative colitis) and healthy control