NOD2 and Cowden disease: On the other hand, genes involved in intestinal barrier homeostasis have been associated with IBD susceptibility [56] suggesting a genetic predisposition that is further supported by the observation that up to 40% of first-degree relatives of CD patients display an altered small intestinal permeability [57–62], with significant association with familial CD and NOD2/CARD15 variants [63, 64].