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. 2008 Jan 7;14(1):38-45.
doi: 10.3748/wjg.14.38.

Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump

Yvonne Meier  1 , Tina Zodan, Carmen Lang, Roland Zimmermann, Gerd A Kullak-Ublick, Peter J Meier, Bruno Stieger, Christiane Pauli-Magnus
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Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump

Yvonne Meier et al. World J Gastroenterol. .

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.

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Figures

Figure 1
Figure 1
Allelic frequency of the T allele (white panel) and C allele (black panel) of the ABCB11 1331T>C (1331T>C) polymorphism. 21 ICPnew patients (42 alleles); 21 ICPold patients (42 alleles); 42 ICPtotal patients (84 alleles); 20 ICPcontrol patients (40 alleles); 205 Caucasiancontrol patients (410 alleles). Allelic frequencies and ORs are given with 95% CI. Groups were compared with Fisher's exact test.
Figure 2
Figure 2
Bile acid levels in patients harboring different 1331C>T genotypes. TT: two patients; CT: 10 patients; CC: 14 patients.
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