Familial disposition and mutations in the Caspase Recruitment Domain 15 (CARD15) have been associated with an increased risk for Crohn's disease (CD). This study investigated whether these risk factors correlate with colonic gene expression profiles generated by DNA-microarray technology. Tissue specimens from descending colon were obtained during colonoscopy from 45 CD patients (18 from areas with inflammation and 27 from noninflamed areas). Gene profiling analysis was performed using the Human Genome U133 Plus 2.0 GeneChip Array. Patients were classified according to their CARD15 status. Hybridization data were analyzed with dChip software. Nine patients with either one or two CARD15 mutations had no differentially expressed genes, compared to 36 patients with wild- type CARD15. There was only one differentially expressed EST between 8 patients who had familial disposition for inflammatory bowel disease (IBD) and 36 who did not, but hierarchical cluster analysis did not show group homogeneity. We conclude that gene expression profiling of mucosal biopsies from the descending colon of patients with CD could not be correlated with CARD15 status or with familial disposition for IBD.