Details of Disease

General Information of Disease (ID: DISMHS5F)

• Disease Name: Intrahepatic cholestasis of pregnancy
• Synonyms: familial recurrent intrahepatic cholestasis of pregnancy; cholestasis, intrahepatic of pregnancy; familial intrahepatic cholestasis of pregnancy; RICP; pregnancy-related cholestasis; gravidic intrahepatic cholestasis; intrahepatic cholestasis of pregnancy; pregnancy related cholestasis; ICP; recurrent intrahepatic cholestasis of pregnancy
• Definition: A cholestatic disorder characterized by (i) pruritus with onset in the second or third trimester of pregnancy, (ii) elevated serum aminotransferases and bile acid levels, and (iii) spontaneous relief of signs and symptoms within two to three weeks after delivery.
• Disease Hierarchy:
  DISHITDZ: Intrahepatic cholestasis
  DISMHS5F: Intrahepatic cholestasis of pregnancy
• Disease Identifiers:
  MONDO ID: MONDO_0100429
  MESH ID: C535932
  UMLS CUI: C0268318
  MedGen ID: 82788
  Orphanet ID: 69665
  SNOMED CT ID: 235888006

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
FGF19	TTGCH11	Limited	Altered Expression	[1]
GPBAR1	TTSDVTR	Limited	Biomarker	[2]
ABCB4	TTJUXV6	Strong	Genetic Variation	[3]
ABCC2	TTFLHJV	Strong	Biomarker	[4]
GABRA2	TTBMV1G	Strong	Biomarker	[5]
KLB	TTARBVH	Strong	Altered Expression	[1]
NR1H4	TTS4UGC	Strong	Genetic Variation	[6]
SLC10A1	TTWZRY5	Strong	Biomarker	[7]
SLCO1A2	TTUGD21	Strong	Altered Expression	[8]
VCAM1	TTHCEF6	Strong	Altered Expression	[9]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
GPT	DER5HFI	Strong	Altered Expression	[10]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ABCG8	OTIJ76XW	Limited	Biomarker	[11]
ERP29	OTNKANMH	Limited	Biomarker	[12]
GGTLC1	OTWJKUHQ	Limited	Biomarker	[13]
ANGPTL8	OTQFINCD	Strong	Altered Expression	[14]
ATP8B1	OTALGS63	Strong	Genetic Variation	[15]
FETUB	OT7V07NI	Strong	Biomarker	[16]
KIFC3	OTOPD4QO	Strong	Biomarker	[5]
POU2F3	OTIOOJWD	Strong	Biomarker	[17]
PTGES3	OTPPQWI0	Strong	Genetic Variation	[18]
PUM1	OTTMWP8L	Strong	Altered Expression	[19]
TJP2	OTQUY6BV	Strong	Biomarker	[15]
TMED10	OTUXSHH7	Strong	Genetic Variation	[18]

References

• [1] Evaluation of FGF-19 and -klotho as biomarkers in patients with intrahepatic cholestasis of pregnancy.Arch Med Sci. 2019 Jan;15(1):113-119. doi: 10.5114/aoms.2017.72424. Epub 2018 Jan 10.
• [2] Bile acids evoke placental inflammation by activating Gpbar1/NF-B pathway in intrahepatic cholestasis of pregnancy.J Mol Cell Biol. 2016 Dec;8(6):530-541. doi: 10.1093/jmcb/mjw025. Epub 2016 Jul 8.
• [3] ABCB4 disease: Many faces of one gene deficiency.Ann Hepatol. 2020 Mar-Apr;19(2):126-133. doi: 10.1016/j.aohep.2019.09.010. Epub 2019 Oct 31.
• [4] Clinical, Pathologic, and Genetic Features of Neonatal Dubin-Johnson Syndrome: A Multicenter Study in Japan.J Pediatr. 2018 May;196:161-167.e1. doi: 10.1016/j.jpeds.2017.12.058. Epub 2018 Feb 28.
• [5] Intrahepatic cholestasis of pregnancy: new insights into its pathogenesis.J Matern Fetal Neonatal Med. 2013 Sep;26(14):1410-5. doi: 10.3109/14767058.2013.783810. Epub 2013 Apr 22.
• [6] Nuclear receptor variants in liver disease.Dig Dis. 2015;33(3):415-9. doi: 10.1159/000371695. Epub 2015 May 27.
• [7] Intrahepatic Cholestasis of Pregnancy as a Clinical Manifestation of Sodium-Taurocholate Cotransporting Polypeptide Deficiency.Tohoku J Exp Med. 2019 May;248(1):57-61. doi: 10.1620/tjem.248.57.
• [8] Bile acid transport correlative protein mRNA expression profile in human placenta with intrahepatic cholestasis of pregnancy.Saudi Med J. 2009 Nov;30(11):1406-10.
• [9] Cholestatic pregnancy is associated with reduced VCAM1 expression in vascular endothelial cell of placenta. Reprod Toxicol. 2017 Dec;74:23-31. doi: 10.1016/j.reprotox.2017.08.002. Epub 2017 Aug 26.
• [10] Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy with dichorionic diamniotic twin pregnancies.J Matern Fetal Neonatal Med. 2019 Feb;32(3):472-476. doi: 10.1080/14767058.2017.1384461. Epub 2017 Oct 11.
• [11] Hepatic expression of detoxification enzymes is decreased in human obstructive cholestasis due to gallstone biliary obstruction.PLoS One. 2015 Mar 23;10(3):e0120055. doi: 10.1371/journal.pone.0120055. eCollection 2015.
• [12] ERp29 inhibition attenuates TCA toxicity via affecting p38/p53- dependent pathway in human trophoblast HTR-8/SVeno cells.Arch Biochem Biophys. 2019 Nov 15;676:108125. doi: 10.1016/j.abb.2019.108125. Epub 2019 Oct 3.
• [13] A new splicing site mutation of the ABCB4 gene in intrahepatic cholestasis of pregnancy with raised serum gamma-GT.Dig Liver Dis. 2009 Sep;41(9):671-5. doi: 10.1016/j.dld.2008.12.101. Epub 2009 Mar 3.
• [14] Assessment of circulating betatrophin levels in intrahepatic cholestasis of pregnancy.J Matern Fetal Neonatal Med. 2019 Dec;32(24):4067-4072. doi: 10.1080/14767058.2018.1481382. Epub 2018 Jun 11.
• [15] An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy.Sci Rep. 2017 Sep 18;7(1):11823. doi: 10.1038/s41598-017-11626-x.
• [16] Increased levels of the novel hepatokine fetuin B in patients with intrahepatic cholestasis of pregnancy.J Matern Fetal Neonatal Med. 2019 May;32(10):1620-1625. doi: 10.1080/14767058.2017.1413546. Epub 2017 Dec 12.
• [17] Role of the placenta in serum autotaxin elevation during maternal cholestasis.Am J Physiol Gastrointest Liver Physiol. 2018 Sep 1;315(3):G399-G407. doi: 10.1152/ajpgi.00112.2018. Epub 2018 Jun 21.
• [18] Maternal susceptibility locus for obstetric cholestasis maps to chromosome region 2p13 in Finnish patients.Scand J Gastroenterol. 2001 Jul;36(7):766-70. doi: 10.1080/003655201300192049.
• [19] Identification of genes for normalization of real-time RT-PCR data in placental tissues from intrahepatic cholestasis of pregnancy.Placenta. 2016 Dec;48:133-135. doi: 10.1016/j.placenta.2016.10.017. Epub 2016 Nov 2.