Cystic fibrosis transmembrane conductance regulator gene polymorphisms in patients with primary sclerosing cholangitis

Background/Aims Primary sclerosing cholangitis (PSC) is a progressive cholestatic disease commonly associated with inflammatory bowel disease (IBD) and characterized by fibrosing inflammatory destruction of bile ducts. The histological features in the liver of PSC patients are similar to those observed in cystic fibrosis (CF). Our aim was to study whether variants in the CFTR gene are associated with the occurrence and/or evolution of PSC. Methods PSC patients ( n = 140) were genotyped for F508del, the TGmTn variants, and four additional polymorphic loci (1001+11 C > T, M470V, T854T and Q1463Q), and compared to 136 matched healthy controls. Results The 1540G-allele, encoding V470, was less frequent in PSC (52%) than in controls (64%, p = 0.003), and was associated with protection against PSC in individuals without IBD (OR 0.25, 95% CI 0.12–0.52, p = 0.0002). Also TG11-T7 was less frequent in PSC (53%) than in controls (61%, p = 0.04), this haplotype was associated with reduced risk for PSC (OR 0.34, 95% CI 0.17–0.70, p = 0.003) in individuals without IBD. Conclusions In this cohort of PSC patients, several CFTR-variants affecting the functional properties of the CFTR protein seem to offer protection against the development of PSC, confirming our hypothesis that CFTR might be implicated in the pathogenesis of PSC.