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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-5274

Meier, Y; Zodan, T; Lang, C; Zimmermann, R; Kullak-Ublick, G A; Meier, P J; Stieger, B; Pauli-Magnus, C (2008). Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump. World Journal of Gastroenterology, 14(1):38-45.

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Abstract

AIM: To study the association of three common ABCB11 and ABCC2 polymorphisms (ABCB11: 1331T>C --> V444A; ABCC2: 3563T>A --> V1188E and 4544G>A --> C1515Y) with intrahepatic cholestasis of pregnancy (ICP) and contraceptive-induced cholestasis (CIC). METHODS: ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS: The ABCB11 1331T>C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls: C allele 76.2% (CI, 58.0-94.4) vs 51.3% (CI 35.8-66.7), respectively (P = 0.0007); and CC allele 57.1% (CI 36.0-78.3) vs 20% (CI 7.6-32.4), respectively (P = 0.0065). All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION: Our data support a role for the ABCB11 1331T>C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and gamma-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Obstetrics
DDC:610 Medicine & health
Language:English
Date:07 January 2008
Deposited On:28 Nov 2008 15:15
Last Modified:27 Nov 2013 23:02
Publisher:WJG Press
ISSN:1007-9327
Publisher DOI:10.3748/wjg.14.38
PubMed ID:18176959
Citations:Web of Science®. Times Cited: 52
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