ABCB4 gene mutations and single-nucleotide polymorphisms in women with intrahepatic cholestasis of pregnancy

Bacq, Yannick; Gendrot, Chantal; Perrotin, Franck; Lefrou, Laurent; Chrétien, Stéphanie; Vie-buret, Véronique; Bréchot, M.C.; Andres, Christian R.

doi:10.1136/jmg.2009.067397

Cited by 68 publications

(34 citation statements)

References 28 publications

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“…Patients with PFIC-III display elevated serum ␥-glutamyltranspeptidase levels and marked bile duct proliferation. In addition, variants of ABCB4 are associated with the severe form of cholestasis of pregnancy, rare cases of juvenile cholesterol gallstones, and drug-induced hepatocellular and cholestatic injury (Lang et al, 2007;Wasmuth et al, 2007;Nakken et al, 2009;Bacq et al, 2009).…”

Section: Apical Efflux Transporters In Livermentioning

confidence: 99%

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

2010

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Section: Apical Efflux Transporters In Livermentioning

confidence: 99%

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

2010

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“…Heterozygous ABCB4 mutations were also identified in up to 15% of women suffering from ICP. 12,20,[21][22][23][24][25][26][27][28][29][30][31] ICP is a reversible form of cholestasis that may develop in the third trimester of pregnancy, usually rapidly resolves after delivery and recurs in 45-70% of subsequent pregnancies. 27 The main symptoms are pruritus and, to a lesser extent, jaundice.…”

mentioning

confidence: 99%

First description of ABCB4 gene deletions in familial low phospholipid-associated cholelithiasis and oral contraceptives-induced cholestasis

et al. 2011

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The wide clinical spectrum of the ABCB4 gene (ATP-binding cassette subfamily B member 4) deficiency syndromes in humans includes low phospholipid-associated cholelithiasis (LPAC), intrahepatic cholestasis of pregnancy (ICP), oral contraceptivesinduced cholestasis (CIC), and progressive familial intrahepatic cholestasis type 3 (PFIC3). No ABCB4 mutations are found in a significant proportion of patients with these syndromes. In the present study, 102 unrelated adult patients with LPAC (43 patients) or CIC/ICP (59 patients) were screened for ABCB4 mutations using DNA sequencing. Heterozygous ABCB4 point or short insertion/deletion mutations were found in 37% (16/43) of the LPAC patients and in 27% (16/59) of the ICP/CIC patients. High-resolution gene dosage methodologies were used in the 70 negative patients. Here, we describe for the first time ABCB4 partial or complete heterozygous deletions in 7% (3/43) of the LPAC patients, and in 2% (1/59) of the ICP/CIC patients. Our observations urge to systematically test patients with LPAC, ICP/CIC, and also children with PFIC3 for the presence of ABCB4 deletions using molecular tools allowing detection of gross rearrangements. In clinical practice, a comprehensive ABCB4 alteration-screening algorithm will permit the use of ABCB4 genotyping to confirm the diagnosis of LPAC or ICP/CIC, and allow familial testing. An early diagnosis of these biliary diseases may be beneficial because of the preventive effect of ursodeoxycholic acid on biliary complications. Further comparative studies of patients with well-characterized genotypes (including deletions) and phenotypes will help determine whether ABCB4 mutation types influence clinical outcomes.

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“…Furthermore, accumulating genetic data show geographic variability regarding the relative importance of the different genes. Whereas ABCB4 mutations were found in 16% of the patients in a French ICP study [49], the corresponding number in Italy was 3-7% [18,19,50]. In a large study of 491 European ICP cases, Dixon et al…”

Section: Gallstones Intrahepatic Cholestasis Of Pregnancy and Drug-imentioning

confidence: 96%

Genetics of cholestatic liver disease in 2010

Karlsen¹,

Hov²

2010

Current Opinion in Gastroenterology

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ABCB4 gene mutations and single-nucleotide polymorphisms in women with intrahepatic cholestasis of pregnancy

Abstract: 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.

Cited by 68 publications

References 28 publications

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

First description of ABCB4 gene deletions in familial low phospholipid-associated cholelithiasis and oral contraceptives-induced cholestasis

Genetics of cholestatic liver disease in 2010

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