Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's disease

Abnormal barrier function may be genetically determined in Crohn's disease. To examine the role of abnormal intestinal permeability in genetic predisposition in multiplex vs. sporadic Crohn's disease families. Intestinal permeability was measured in patients, relatives and partners by means of lactulose/mannitol test. Healthy subjects from the hospital staff served as controls. CARD15 mutations were investigated in sporadic and familial Crohn's disease patients and in a group of blood donors. The median lactulose/mannitol ratio was increased significantly in Crohn's disease patients vs. their relatives [0.03 (0.01-0.24) vs. 0.01 (0.003-0.19), P = 0.005]. The percentage of abnormal tests was significantly higher in familial vs. sporadic first-degree relatives of Crohn's disease patients (29% vs. 11%, P = 0.0281). Abnormal permeability occurred significantly more frequent in patients with familial Crohn's disease carrying the frameshift mutation. The frameshift mutation 3020msC was associated with increased permeability in 75% in the multiplex and in 61% of the sporadic CD patients. One partner had abnormal lactulose/mannitol ratio. Intestinal permeability is raised in Crohn's disease patients and relatives, with higher rates in familial vs. sporadic healthy relatives. CARD15 mutations are associated with abnormal permeability in ileal Crohn's disease.