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Review
. 2024 Sep;17(3):157-161.
doi: 10.1177/1753495X241263441. Epub 2024 Jul 26.

Genetic issues in ICP

Julia Zöllner  1 , Catherine Williamson  2 , Peter H Dixon  2
Affiliations
Review

Genetic issues in ICP

Julia Zöllner et al. Obstet Med. 2024 Sep.

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is the commonest gestational liver disorder with variable global incidence. Genetic susceptibility, combined with hormonal and environmental influences, contributes to ICP aetiology. Adverse pregnancy outcomes linked to elevated serum bile acids highlight the importance of comprehensive risk assessment. ABCB4 and ABCB11 gene variants play a significant role in about 20% of severe ICP cases. Several other genes including ATP8B1, NR1H4, ABCC2, TJP2, SERPINA1, GCKR and HNF4A have also been implicated with ICP. Additionally, ABCB4 variants elevate the risk of drug-induced intrahepatic cholestasis, gallstone disease, gallbladder and bile duct carcinoma, liver cirrhosis and abnormal liver function tests. Genetic variations, both rare and common, intricately contribute to ICP susceptibility. Leveraging genetic insights holds promise for personalised management and intervention strategies. Further research is needed to elucidate variant-specific phenotypic expressions and therapeutic implications, advancing precision medicine in ICP management.

Keywords: Intrahepatic cholestasis of pregnancy; genetics; genomics; pregnancy complications.

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Conflict of interest statement

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CW consults for Mirum and GSK.

Figures

Figure 1.
Figure 1.
The role of canalicular transporters or their regulators implicated in the pathogenesis of ICP.
See this image and copyright information in PMC

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