OBJECTIVE: To determine whether primary sclerosing cholangitis (PSC) in childhood is associated with abnormalities in cystic fibrosis transmembrane conductance regulator (CFTR). STUDY DESIGN: Subjects with PSC diagnosed in childhood (n = 20) were recruited from Children's Hospital. Subjects had testing with sweat chloride concentration, nasal transmembrane potential difference, and extensive genetic analysis of the CFTR gene. Disease control subjects consisted of 14 patients with inflammatory bowel disease alone and no liver disease. t tests were performed to determine statistical significance. RESULTS: In the PSC group, CFTR chloride channel function (deltaChloride free + isoproterenol) was markedly diminished at -8.6 +/- 8.2 mV (reference range: -24.6 +/- 10.4 mV). In contrast, disease control subjects had normal function, at -17.8 +/- 9.7 mV (P = .008). Sweat chloride concentration in subjects with PSC was greater than in disease control subjects (20.8 +/- 3.4 mmol/L vs 12.0 +/- 1.6 mmol/L, P = .045). Comprehensive CFTR genotyping revealed that 5 of 19 (26.3%) subjects with PSC had a CFTR mutation or variant, compared with 6 of 14 (42.9%) disease control subjects. CONCLUSIONS: There is a high prevalence of CFTR-mediated ion transport dysfunction in subjects with childhood PSC.
OBJECTIVE: To determine whether primary sclerosing cholangitis (PSC) in childhood is associated with abnormalities in cystic fibrosis transmembrane conductance regulator (CFTR). STUDY DESIGN: Subjects with PSC diagnosed in childhood (n = 20) were recruited from Children's Hospital. Subjects had testing with sweat chloride concentration, nasal transmembrane potential difference, and extensive genetic analysis of the CFTR gene. Disease control subjects consisted of 14 patients with inflammatory bowel disease alone and no liver disease. t tests were performed to determine statistical significance. RESULTS: In the PSC group, CFTRchloride channel function (deltaChloride free + isoproterenol) was markedly diminished at -8.6 +/- 8.2 mV (reference range: -24.6 +/- 10.4 mV). In contrast, disease control subjects had normal function, at -17.8 +/- 9.7 mV (P = .008). Sweat chloride concentration in subjects with PSC was greater than in disease control subjects (20.8 +/- 3.4 mmol/L vs 12.0 +/- 1.6 mmol/L, P = .045). Comprehensive CFTR genotyping revealed that 5 of 19 (26.3%) subjects with PSC had a CFTR mutation or variant, compared with 6 of 14 (42.9%) disease control subjects. CONCLUSIONS: There is a high prevalence of CFTR-mediated ion transport dysfunction in subjects with childhood PSC.
Authors: C R Martin; P G Blanco; J C Keach; J L Petz; M M Zaman; K R Bhaskar; J E Cluette-Brown; S Gautam; S Sheth; N H Afdhal; K D Lindor; S D Freedman Journal: Aliment Pharmacol Ther Date: 2011-11-30 Impact factor: 8.171
Authors: Camilia R Martin; Munir M Zaman; Gyanprakash A Ketwaroo; Abdul Q Bhutta; Emmanuel Coronel; Yury Popov; Detlef Schuppan; Steven D Freedman Journal: Am J Physiol Gastrointest Liver Physiol Date: 2012-06-07 Impact factor: 4.052
Authors: Johannes R Hov; Verena Keitel; Jon K Laerdahl; Lina Spomer; Eva Ellinghaus; Abdou ElSharawy; Espen Melum; Kirsten M Boberg; Thomas Manke; Tobias Balschun; Christoph Schramm; Annika Bergquist; Tobias Weismüller; Daniel Gotthardt; Christian Rust; Liesbet Henckaerts; Clive M Onnie; Rinse K Weersma; Martina Sterneck; Andreas Teufel; Heiko Runz; Adolf Stiehl; Cyriel Y Ponsioen; Cisca Wijmenga; Morten H Vatn; Pieter C F Stokkers; Severine Vermeire; Christopher G Mathew; Benedicte A Lie; Ulrich Beuers; Michael P Manns; Stefan Schreiber; Erik Schrumpf; Dieter Häussinger; Andre Franke; Tom H Karlsen Journal: PLoS One Date: 2010-08-25 Impact factor: 3.240