Background/aims: The aim of this prospective study was to evaluate the nature and frequency of the ATP binding cassette subfamily B member 4 (ABCB4) gene variants in a series of French patients with intrahepatic cholestasis of pregnancy (ICP).
Methods: The entire ABCB4 gene coding sequence was analyzed by DNA sequencing in 50 unrelated women with ICP defined by pruritus and elevated serum alanine aminotransferases 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: We observed 8 genomic variants. One nonsense mutation (p.Arg144Stop) and 2 missense mutations (p.Ser320Phe and p.Thr775Met) were revealed each in one heterozygous patient. A Third missense mutation (p.Arg590Gln) was detected in 3 heterozygous patients and in 2 homozygous patients also homozygous for a particular haplotype of 3 single nucleotide polymorphisms (c.175C>T, c.504T>C, c.711A>T). The chromosomal frequency of the p.Arg590Gln variant was significantly different between ICP and control groups (7.0 % versus 0.5%; p=0.0017; OR:16.03, 95% CI:1.94-132.16). An association was also found between allele T of the c.504 T>C silent nucleotide polymorphism and ICP (68.0 % versus 53.7%; p=0.017; OR 1.83, 95% CI: 1.08-3.11). The chromosomal frequency of the p.Arg652Gly variant was not different between ICP and control groups (p=0.40).
Conclusion: this study demonstrates that 16% of Caucasian patients suffering from ICP bear ABCB4 gene mutations, and confirms the significant involvement of this gene in the pathogenesis of this complex disorder.
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