title: ABCB4 gene mutations and single-nucleotide polymorphisms in women with intrahepatic cholestasis of pregnancy.
abstract: OBJECTIVE
  To evaluate the nature and frequency of ATP-binding cassette subfamily B member 4 (ABCB4) gene variants in a series of French patients with intrahepatic cholestasis of pregnancy (ICP).
  
  
  METHODS
  In this prospective study, the entire ABCB4 gene coding sequence was analysed by DNA sequencing in 50 unrelated women with ICP defined by pruritus and raised serum alanine aminotransferase activity or bile acid concentration, with recovery after delivery. Genomic variants detected in patients with ICP were sought in 107 control pregnant women. Patients with ICP and controls were of Caucasian origin.
  
  
  RESULTS
  Eight genomic variants were observed. One nonsense mutation (p.Arg144Stop) and two missense mutations (p.Ser320Phe and p.Thr775Met) were revealed each in one heterozygous patient. A third missense mutation (p.Arg590Gln) was detected in three heterozygous patients and in two homozygous patients also homozygous for a particular haplotype of three single-nucleotide polymorphisms (c.175C>T, c.504T>C, c.711A>T). The chromosomal frequency of the p.Arg590Gln variant was significantly different between the ICP and control group (7.0% vs 0.5%; p = 0.0017; OR 16.03, 95% CI 1.94 to 132.16). An association was also found between allele T of the c.504T>C silent nucleotide polymorphism and ICP (68.0% vs 53.7%; p = 0.017; OR 1.83, 95% CI 1.08 to 3.11). The chromosomal frequency of the p.Arg652Gly variant did not differ between the ICP and control group (p = 0.40).
  
  
  CONCLUSIONS
  This study shows that 16% of Caucasian patients with ICP bear ABCB4 gene mutations, and confirms the significant involvement of this gene in the pathogenesis of this complex disorder.
authors: Y
authors: Y
authors: Bacq
authors: C
authors: C
authors: Gendrot
authors: F
authors: F
authors: Perrotin
authors: L
authors: L
authors: Lefrou
authors: S
authors: S
authors: Chrétien
authors: V
authors: V
authors: Vie-Buret
authors: M-C
authors: MC
authors: Brechot
authors: C R
authors: CR
authors: Andres
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D002780:Cholestasis, Intrahepatic / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics*; D011446:Prospective Studies; D016415:Sequence Alignment
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; C095122:multidrug resistance protein 3