TUCAN (CARD8) genetic variants and inflammatory bowel disease

Background & AiMS: The identification of the association between Crohn's disease (CD) and NOD2 (CARD15) confirmed both the heritability of CD and highlighted the role of the nuclear factor kappa B (NF kappa B) pathway in disease pathogenesis. other susceptibility loci exist. TUCAN (CARD8) is located beneath a CD peak of linkage on chromosome 19q. TUCAN is expressed in the gut and is a negative regulator of NF kappa B, making it an excellent candidate gene for gastrointestinal inflammation. Methods: Ten single nucleotide polymorphisms (SNP) across TUCAN were genouyped in 36S controls, 372 patients with CD, and 373 patients with ulcerative colitis. A diagnostic panel for CD was constructed using smoking status and TUCAN, NOD2, IBD5, NOD1, and TNFSF15 data. Results: We demonstrate significant association between a TUCAN SNP and CD (OR 1.35, P =.0083). The association was more pronounced with disease affecting sites other than the colon (odds ratio, 1.52) and NOD2-negative CD (odds ratio, 130). Combination of these data with smoking and NOD2, IBD5, NOD1, and TNFSF15 status demonstrated very strong associations with CD and high sensitivities (96.3%), specificities (99.4%), and likelihood ratios (12.8) for CD, although further work will be needed before this model can be translated into direct clinical utility. Conclusions: We have shown an association between a likely functional polymorphism in 7TUCAN and CD. The combination of these data in a genetic panel suggests that clinicians may soon be able to translate genetic advances into direct benefits for patients.