Article: Increased prevalence of CFTR mutations and variants and decreased chloride secretion in primary sclerosing cholangitis

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TitleIncreased prevalence of CFTR mutations and variants and decreased chloride secretion in primary sclerosing cholangitis
AuthorsSheth, S1
Shea, JC1
Bishop, MD1
Chopra, S1
Regan, MM1
Malmberg, E2
Walker, C2
Ricci, R2
Tsui, LC2
Durie, PR2
Zielenski, J2
Freedman, SD1
Issue Date2003
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htm
CitationHuman Genetics, 2003, v. 113 n. 3, p. 286-292 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00439-003-0963-z
AbstractPrimary sclerosing cholangitis (PSC) and cystic fibrosis (CF) are both slowly progressive cholestatic liver diseases characterized by fibro-obliterative inflammation of the biliary tract. We hypothesized that dysfunction of the CF gene product, cystic fibrosis transmembrane conductance regulator (CFTR), may explain why a subset of patients with inflammatory bowel disease develop PSC. We prospectively evaluated CFTR genotype and phenotype in patients with PSC (n=19) compared with patients with inflammatory bowel disease and no liver disease (n=18), primary biliary cirrhosis (n=17), CF (n=81), and healthy controls (n=51). Genetic analysis of the CFTR gene in PSC patients compared with disease controls (primary biliary cirrhosis and inflammatory bowel disease) demonstrated a significantly increased number of mutations/variants in the PSC group (37% vs 8.6% of disease controls, P=0.02). None of the PSC patients carried two mutations/variants. Of PSC patients, 89% carried the 1540G-variant-containing genotypes (resulting in decreased functional CFTR) compared with 57% of disease controls (P=0.03). Only one of 19 PSC patients had neither a CFTR mutation nor the 1540G variant. CFTR chloride channel function assessed by nasal potential difference testing demonstrated a reduced median isoproterenol response of 14 mV in PSC patients compared with 19mV in disease controls (P=0.04) and 21 mV in healthy controls (P=0.003). These data indicate that there is an increased prevalence of CFTR abnormalities in PSC as demonstrated by molecular and functional analyses and that these abnormalities may contribute to the development of PSC in a subset of patients with inflammatory bowel disease. © Springer-Verlag 2003.
ISSN0340-6717
2011 Impact Factor: 5.069
2011 SCImago Journal Rankings: 0.328
DOIhttp://dx.doi.org/10.1007/s00439-003-0963-z
ISI Accession Number IDWOS:000184807600013
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorSheth, S
dc.contributor.authorShea, JC
dc.contributor.authorBishop, MD
dc.contributor.authorChopra, S
dc.contributor.authorRegan, MM
dc.contributor.authorMalmberg, E
dc.contributor.authorWalker, C
dc.contributor.authorRicci, R
dc.contributor.authorTsui, LC
dc.contributor.authorDurie, PR
dc.contributor.authorZielenski, J
dc.contributor.authorFreedman, SD
dc.date.accessioned2007-09-12T03:52:29Z
dc.date.available2007-09-12T03:52:29Z
dc.date.issued2003
dc.description.abstractPrimary sclerosing cholangitis (PSC) and cystic fibrosis (CF) are both slowly progressive cholestatic liver diseases characterized by fibro-obliterative inflammation of the biliary tract. We hypothesized that dysfunction of the CF gene product, cystic fibrosis transmembrane conductance regulator (CFTR), may explain why a subset of patients with inflammatory bowel disease develop PSC. We prospectively evaluated CFTR genotype and phenotype in patients with PSC (n=19) compared with patients with inflammatory bowel disease and no liver disease (n=18), primary biliary cirrhosis (n=17), CF (n=81), and healthy controls (n=51). Genetic analysis of the CFTR gene in PSC patients compared with disease controls (primary biliary cirrhosis and inflammatory bowel disease) demonstrated a significantly increased number of mutations/variants in the PSC group (37% vs 8.6% of disease controls, P=0.02). None of the PSC patients carried two mutations/variants. Of PSC patients, 89% carried the 1540G-variant-containing genotypes (resulting in decreased functional CFTR) compared with 57% of disease controls (P=0.03). Only one of 19 PSC patients had neither a CFTR mutation nor the 1540G variant. CFTR chloride channel function assessed by nasal potential difference testing demonstrated a reduced median isoproterenol response of 14 mV in PSC patients compared with 19mV in disease controls (P=0.04) and 21 mV in healthy controls (P=0.003). These data indicate that there is an increased prevalence of CFTR abnormalities in PSC as demonstrated by molecular and functional analyses and that these abnormalities may contribute to the development of PSC in a subset of patients with inflammatory bowel disease. © Springer-Verlag 2003.
dc.description.natureabstract
dc.identifier.citationHuman Genetics, 2003, v. 113 n. 3, p. 286-292 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00439-003-0963-z
dc.identifier.doihttp://dx.doi.org/10.1007/s00439-003-0963-z
dc.identifier.epage292
dc.identifier.isiWOS:000184807600013
dc.identifier.issn0340-6717
2011 Impact Factor: 5.069
2011 SCImago Journal Rankings: 0.328
dc.identifier.issue3
dc.identifier.pmid12783301
dc.identifier.scopuseid_2-s2.0-0041563992
dc.identifier.spage286
dc.identifier.urihttp://hdl.handle.net/10722/44383
dc.identifier.volume113
dc.languageeng
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htm
dc.publisher.placeGermany
dc.relation.ispartofHuman Genetics
dc.relation.referencesReferences in Scopus
dc.rightsThe original publication is available at www.springerlink.com
dc.subject.meshBiology - genetics
dc.subject.meshChlorides - metabolism
dc.subject.meshCholangitis, sclerosing - genetics - metabolism
dc.subject.meshCystic fibrosis transmembrane conductance regulator - genetics
dc.subject.meshInflammatory bowel diseases - genetics
dc.titleIncreased prevalence of CFTR mutations and variants and decreased chloride secretion in primary sclerosing cholangitis
dc.typeArticle
Author Affiliations
  1. Harvard Medical School
  2. Hospital for Sick Children, Toronto