title: Intrahepatic cholestasis of pregnancy: three novel MDR3 gene mutations.
abstract: BACKGROUND
  The aetiology of intrahepatic cholestasis of pregnancy is unknown, but more than 10 different MDR3 gene mutations have recently been identified.
  
  
  OBJECTIVE
  To evaluate the genetic contribution of the MDR3 gene in the pathogenesis of intrahepatic cholestasis of pregnancy in Italian subjects.
  
  
  METHODS
  We performed a multicentre prospective case-control study, enrolling 80 women with intrahepatic cholestasis of pregnancy at the third trimester of pregnancy and 80 pregnant women without intrahepatic cholestasis of pregnancy. Genomic DNA was extracted from peripheral venous blood leucocytes using standard procedures. The polymerase chain reaction was used to amplify exon 14 of the MDR3 gene and the polymerase chain reaction products were sequenced using a Big Dye Terminator Cycle Sequencing kit.
  
  
  RESULTS
  Three novel non-synonymous heterozygous mutations in exon 14 were found (4%; E528D, R549H, G536R) among the 80 intrahepatic cholestasis of pregnancy patients, whereas the pregnant controls were all negative for exon 14 polymorphisms. The three patients involved had normal GGT and bilirubin, but high levels of both ALT and serum bile acids. One had cholesterol bile stones. The outcome of pregnancy was normal for two (with vaginal delivery), while foetal distress was recorded in the third.
  
  
  CONCLUSIONS
  These three novel mutations add further information on the involvement of the MDR3 gene in intrahepatic cholestasis of pregnancy. As in other studies, we found only heterozygous mutations that could cause an impaired transport protein function, not its absence (which is responsible for more severe liver disease). Different genetic backgrounds might justify the presence of novel MDR3 gene mutations.
authors.affiliation: Department of Surgical and Gastroenterological Sciences, University of Padova, Padova, Italy. annarosa.floreani@unipd.it
authors.forename: A
authors.initials: A
authors.lastname: Floreani
authors.forename: I
authors.initials: I
authors.lastname: Carderi
authors.forename: D
authors.initials: D
authors.lastname: Paternoster
authors.forename: G
authors.initials: G
authors.lastname: Soardo
authors.forename: F
authors.initials: F
authors.lastname: Azzaroli
authors.forename: W
authors.initials: W
authors.lastname: Esposito
authors.forename: A
authors.initials: A
authors.lastname: Variola
authors.forename: A M
authors.initials: AM
authors.lastname: Tommasi
authors.forename: D
authors.initials: D
authors.lastname: Marchesoni
authors.forename: C
authors.initials: C
authors.lastname: Braghin
authors.forename: G
authors.initials: G
authors.lastname: Mazzella
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D016022:Case-Control Studies; D002780:Cholestasis, Intrahepatic / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics*; D011256:Pregnancy Outcome; D011446:Prospective Studies
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1