title: ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population.
abstract: BACKGROUND
  Genetic alterations in the ATP-binding cassette subfamily B member 4 (ABCB4) and ATP-binding cassette subfamily B member 11 (ABCB11) have been associated to the onset of intrahepatic cholestasis of pregnancy (ICP) in predisposed women.
  
  
  OBJECTIVE
  To identify new and/or frequent ABCB4 and ABCB11 genes variants in a cohort of Italian patients with ICP and to evaluate the possible pathogenetic role for the novel mutations identified.
  
  
  METHODS
  DNA of 33 unrelated Italian women with obstetric cholestasis were screened for mutations in the entire coding sequence of ABCB4 and ABCB11 genes. Polymerase chain reaction and automated sequencing was performed on the 27 coding exons of both genes.
  
  
  RESULTS
  Genotyping revealed 11 mutations, 5 of whom were novel variants: 2 localized on ABCB4 (p.I587DfsX603, p.I738LfsX744) and 3 on ABCB11 (p.V284D, p.Q558H, p.P731S). The most severe phenotypes were associated with the variants p.I587DfsX603, p.I738LfsX744 and p.V284D. Moreover, the already described mutation p.N510S found in ABCB4 seems to be strictly involved in the onset of ICP in that particular patient.
  
  
  CONCLUSIONS
  Our data support the hypothesis of a significant involvement of ABCB4 mutations in the onset of ICP, but also confirm an important role for ABCB11 mutations in increasing the susceptibility to cholestasis of pregnancy.
authors.affiliation: Department of Medicine, Endocrinology, Metabolism and Geriatrics, University of Modena and Reggio Emilia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Anzivino
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Odoardi
authors.forename: Erica
authors.initials: E
authors.lastname: Meschiari
authors.forename: Enrica
authors.initials: E
authors.lastname: Baldelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchinetti
authors.forename: Isabella
authors.initials: I
authors.lastname: Neri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ruggiero
authors.forename: Rosa
authors.initials: R
authors.lastname: Zampino
authors.forename: Marco
authors.initials: M
authors.lastname: Bertolotti
authors.forename: Paola
authors.initials: P
authors.lastname: Loria
authors.forename: Lucia
authors.initials: L
authors.lastname: Carulli
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D002780:Cholestasis, Intrahepatic / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D009154:Mutation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000208:ethnology / Q000235:genetics*; D012720:Severity of Illness Index; D044465:White People
chemical_list: C093491:ABCB11 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C095122:multidrug resistance protein 3