NOD2 and Cowden disease: Indeed, DMBT1 shows increased expression in the intestinal mucosa in CD patients, and this increased expression is dependent on NOD2 activation, because this response is abolished in CD patients homozygous for a NOD2 SNP allele causing a NOD2 frameshift, an allele also associated with CD.28 Given the role of DMBT1 in binding bacteria,29, 30 it seems reasonable to assume that the DMBT1SR47− deletion allele encodes a protein that has an altered interaction with the intestinal flora, and mediates its effect via its interactions with bacteria.