Objectives: Approximately 80% of patients with primary sclerosing cholangitis (PSC) of Northern European origin have concurrent inflammatory bowel disease (IBD). The majority have ulcerative colitis, but there is also an association with Crohn's colitis. The pathogenetic link between PSC and IBD is unknown. We aimed to assess whether genetic risk factors in PSC can be identified on the basis of known IBD susceptibility genes and the shared PSC-IBD phenotype.
Methods: IBD-associated polymorphisms in the CARD15, TLR-4, CARD4, SLC22A4, SLC22A5, DLG5, and MDR1 genes were genotyped in a large cohort of 365 Scandinavian PSC patients and 368 healthy controls using TaqMan technology.
Results: No significant association between any of the investigated genetic IBD risk variants and overall susceptibility to PSC was observed. Apart from a tendency toward an increased carrier frequency of the mutant CARD15 alleles in PSC patients with concurrent Crohn's disease as compared with healthy controls (15.6%vs 9.0%, P = 0.22), no association with any of the polymorphisms investigated was evident even when considering only PSC patients with concurrent IBD.
Conclusion: It seems unlikely that IBD-associated polymorphisms in the CARD15, TLR-4, CARD4, SLC22A4, SLC22A5, DLG5, and MDR1 genes confer susceptibility to PSC. The current knowledge of genetic risk factors in IBD may not contribute to our understanding of molecular mechanisms involved in the pathogenesis of PSC or the IBD phenotype in PSC.