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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
2013 Impact Factor: 4.522
 
DOIhttp://dx.doi.org/10.1007/s00439-003-0963-z
 
ISI Accession Number IDWOS:000184807600013
 
ReferencesReferences in Scopus
 
DC FieldValue
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
2013 Impact Factor: 4.522
 
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
 
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Author Affiliations
  1. Harvard Medical School
  2. Hospital for Sick Children University of Toronto