title: Does the mutation of the SERPINA1 gene contribute to liver damage and cholestasis in patients with diagnosed cystic fibrosis? preliminary study.
abstract: Mutation of the SERPINA1 gene is present in about 2% of patients with cystic fibrosis but is more common and accounts for about 5% in patients with cystic fibrosis and co-existing liver lesions. The SERPINA1 gene is responsible for the synthesis of a serine protease inhibitor. The protein related with this gene is accumulated within the endoplasmic reticulum of hepatocytes causing their damage, inflammation and cirrhosis. The aim was to assess the presumable effect of the SERPINA1 mutation gene in patients with diagnosed cystic fibrosis on damage to the liver and/or cholestasis.
  
  
  METHODS
  The analysis included 30 children, 13 girls (43.3%) and 17 boys (56.6%), aged from 6 months to 18 years (the average age was 5.5 years) with diagnosed cystic fibrosis. All the patients have undergone a genetic test of the mutation of the SERPINA1 gene. The analysis included age, sex, clinical symptoms, type of mutation of the CFTR protein, abnormalities in laboratory tests (the activity of aminotransferases, GGTP, alkaline phosphatase , protein, the indicator of acid steatocrit, the rate of APRI) and abdominal ultrasonography.
  
  
  RESULTS
  Symptoms of damaged liver were concluded in 9/30 patients (30%) with diagnosed cystic fibrosis. Most commonly observed were increased activities of aminotransferases in 9/30 patients (30%) and of gamma glutamyl transferase in 6/30 (20%) of the assessed patients. In 4/30 patients the abdominal ultrasonography revealed an enlarged liver and increased echogenicity. Mutation within the SERPINA1 gene was observed only in 1/30 patients (3.3%) with diagnosed cystic fibrosis. As far as the patient is concerned, currently the activities of aminotransferases, GGTP and AF are normal, but there has been a considerable increase in the intensity of symptoms from the respiratory system. No corelation between the mutation of the SERPINA1 gene and clinical symptoms, type of mutation of the CFTR protein, laboratory results of the functions and damage to the liver and the abdominal ultrasonography was observed.
  
  
  CONCLUSIONS
  We did not find a more frequent occurrence of the SERPINA1 gene mutation in children with cystic fibrosis and coexisting features of damaged liver and cholestasis. The obtained results suggest the contribution of other than SERPINA1 gene mutation factors responsible for the development of changes in the liver in patients diagnosed with cystic fibrosis. The studies on the subject should be extended and performed on a larger group of patients. .
authors.affiliation: Department of Paediatrics, Medical University of Silesia, 16 Medykow Street, 40-752 Katowice, Poland, e-mail: sabinawk@wp.pl.
authors.forename: Sabina
authors.initials: S
authors.lastname: Więcek
authors.forename: Halina
authors.initials: H
authors.lastname: Woś
authors.forename: Bożena
authors.initials: B
authors.lastname: Kordys-Darmolińska
authors.forename: Magda
authors.initials: M
authors.lastname: Sankiewicz-Szkółka
authors.forename: Urszula
authors.initials: U
authors.lastname: Grzybowska-Chlebowczyk
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002779:Cholestasis / Q000235:genetics*; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008107:Liver Diseases / Q000235:genetics*; D008297:Male; D009154:Mutation; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator