title: An MBL2 haplotype and ABCB4 variants modulate the risk of liver disease in cystic fibrosis patients: a multicentre study.
abstract: BACKGROUND
  Cystic fibrosis is the most common lethal recessive disorder among Caucasians. Over 1500 mutations have been identified in cystic fibrosis transmembrane conductance regulator disease-gene so far. A large variability of the clinical phenotype has been observed both in cystic fibrosis patients bearing the same genotype, and in affected sibpairs. Thus, genes inherited independently from cystic fibrosis transmembrane conductance regulator could modulate the clinical expression of cystic fibrosis.
  
  
  METHODS
  We analysed some putative modifier genes of liver cystic fibrosis phenotype (serpin 1, hemochromatosis, transferrin receptor 2, ferroportin 1, mannose binding lectin and adenosine triphospate-binding cassette subfamily B member 4) in 108 unrelated cystic fibrosis patients with and without liver involvement.
  
  
  RESULTS
  HYPD mannose binding lectin haplotype was significantly (p<0.05) more frequent in cystic fibrosis patients with liver disease versus those without liver disease. This haplotype already related to a more severe pulmonary cystic fibrosis phenotype, is associated to a reduced MBL immunological activity. The c.834-66G>T variant of adenosine triphospate-binding cassette subfamily B member 4 gene was significantly (p<0.05) less frequent in cystic fibrosis patients with liver disease as compared to those with no liver disease.
  
  
  CONCLUSIONS
  The HYPD mannose binding lectin haplotype may predispose a subgroup of cystic fibrosis patients to a more severe liver involvement impairing the local defence mechanisms whereas the c.834-66G>T adenosine triphospate-binding cassette subfamily B member 4 variant may enhance the activity of the protein and thus exert a protective effect toward liver disease.
authors.affiliation: Department of Biochemistry and Medical Biotechnology and Faculty of Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Tomaiuolo
authors.forename: D
authors.initials: D
authors.lastname: Degiorgio
authors.forename: D A
authors.initials: DA
authors.lastname: Coviello
authors.forename: A
authors.initials: A
authors.lastname: Baccarelli
authors.forename: A
authors.initials: A
authors.lastname: Elce
authors.forename: V
authors.initials: V
authors.lastname: Raia
authors.forename: V
authors.initials: V
authors.lastname: Motta
authors.forename: M
authors.initials: M
authors.lastname: Seia
authors.forename: G
authors.initials: G
authors.lastname: Castaldo
authors.forename: C
authors.initials: C
authors.lastname: Colombo
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008107:Liver Diseases / Q000150:complications / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; C095122:multidrug resistance protein 3