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

TitleIncreased prevalence of CFTR mutations and variants and decreased chloride secretion in primary sclerosing cholangitis
Authors
Issue Date2003
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htm
Citation
Human Genetics, 2003, v. 113 n. 3, p. 286-292 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/44383
ISSN
2014 Impact Factor: 4.824
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSheth, Sen_HK
dc.contributor.authorShea, JCen_HK
dc.contributor.authorBishop, MDen_HK
dc.contributor.authorChopra, Sen_HK
dc.contributor.authorRegan, MMen_HK
dc.contributor.authorMalmberg, Een_HK
dc.contributor.authorWalker, Cen_HK
dc.contributor.authorRicci, Ren_HK
dc.contributor.authorTsui, LCen_HK
dc.contributor.authorDurie, PRen_HK
dc.contributor.authorZielenski, Jen_HK
dc.contributor.authorFreedman, SDen_HK
dc.date.accessioned2007-09-12T03:52:29Z-
dc.date.available2007-09-12T03:52:29Z-
dc.date.issued2003en_HK
dc.identifier.citationHuman Genetics, 2003, v. 113 n. 3, p. 286-292en_HK
dc.identifier.issn0340-6717en_HK
dc.identifier.urihttp://hdl.handle.net/10722/44383-
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.en_HK
dc.languageengen_HK
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htmen_HK
dc.relation.ispartofHuman Geneticsen_HK
dc.rightsThe original publication is available at www.springerlink.comen_HK
dc.subject.meshBiology - geneticsen_HK
dc.subject.meshChlorides - metabolismen_HK
dc.subject.meshCholangitis, sclerosing - genetics - metabolismen_HK
dc.subject.meshCystic fibrosis transmembrane conductance regulator - geneticsen_HK
dc.subject.meshInflammatory bowel diseases - geneticsen_HK
dc.titleIncreased prevalence of CFTR mutations and variants and decreased chloride secretion in primary sclerosing cholangitisen_HK
dc.typeArticleen_HK
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.natureabstracten_HK
dc.identifier.doi10.1007/s00439-003-0963-zen_HK
dc.identifier.pmid12783301en_HK
dc.identifier.scopuseid_2-s2.0-0041563992en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0041563992&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume113en_HK
dc.identifier.issue3en_HK
dc.identifier.spage286en_HK
dc.identifier.epage292en_HK
dc.identifier.isiWOS:000184807600013-
dc.publisher.placeGermanyen_HK
dc.identifier.scopusauthoridSheth, S=7102603375en_HK
dc.identifier.scopusauthoridShea, JC=7202997283en_HK
dc.identifier.scopusauthoridBishop, MD=7201415929en_HK
dc.identifier.scopusauthoridChopra, S=7202868667en_HK
dc.identifier.scopusauthoridRegan, MM=7103031293en_HK
dc.identifier.scopusauthoridMalmberg, E=36871335700en_HK
dc.identifier.scopusauthoridWalker, C=7402887220en_HK
dc.identifier.scopusauthoridRicci, R=8137911900en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.scopusauthoridDurie, PR=7005360997en_HK
dc.identifier.scopusauthoridZielenski, J=7003732699en_HK
dc.identifier.scopusauthoridFreedman, SD=35514314700en_HK

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