Lack of association of common cystic fibrosis transmembrane conductance regulator gene mutations with primary sclerosing cholangitis.
BACKGROUND
Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease of uncertain etiology. However, the histologic features of PSC liver disease can resemble those in cystic fibrosis (CF), an inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We sought to determine if PSC patients have a higher frequency of common CF alleles than disease controls.


METHODS
DNA was extracted from peripheral lymphocytes of patients with end-stage liver disease. Samples were obtained before liver transplantation from 59 PSC patients and from three groups of control patients (20 each with primary biliary cirrhosis, autoimmune hepatitis, or hepatitis C). DNA samples were genotyped for 32 common CF mutations, the intron 8 T tract variants, and the M470V variant.


RESULTS
One of 59 PSC patients (1.7%) had the common CF mutation (DeltaF508) in one CFTR gene. Two controls (3.3%) carried a single CF mutation (DeltaF508 in one primary biliary cirrhosis patient; W1282X in one hepatitis C patient). These rates do not differ from expected in the general population. The frequency of CFTR variants (5T and M470V) was also similar between PSC patients and controls.


CONCLUSIONS
Despite anatomical similarities between CF liver disease and PSC, we could not confirm that PSC patients carried common CF mutations or common CFTR variants in higher than expected frequencies. These data suggest that CFTR dysfunction does not influence the pathogenesis of PSC.
Gallegos-Orozco
Juan F
JF
Division of Transplantation Medicine, Mayo Clinic, Scottsdale, Arizona 85259, USA.
E Yurk
Catherine
C
Wang
Nulang
N
Rakela
Jorge
J
Charlton
Michael R
MR
Cutting
Garry R
GR
Balan
Vijayan
V
D000328:Adult; D000368:Aged; D000483:Alleles; D001706:Biopsy; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006526:Hepatitis C / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D019693:Hepatitis, Autoimmune / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013223:Statistics as Topic
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator