Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268318 (ICP)
 10,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intrahepatic cholestasis of pregnancy (ICP) is a relatively benign cholestatic pathology of the liver developing in II or III trimester of pregnancy and characterized by itchy skin and enhanced serum bile acid levels. The cause of ICP is unknown; it may have a multifactor nature involving genetic (ABCB4, EXR, ABCC2 genes), hormonal (estrogens, progesterone), and environmental factors. As a rule, ICP first manifests itself on weeks 28-30 of pregnancy in the form of pruritus especially pronounced at night time. Almost half of the patients develop jaundice, usually within 1-4 weeks after appearance of pruritus. The enhanced serum bile acid level is sometimes the first or the sole laboratory sign of the disease. Ursodeoxycholic acid is currently the drug of choice for the treatment of ICP due to its confirmed effectiveness and safety.
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PMID:[INTRAHEPATIC CHOLESTASIS OF PREGNANCY: STATE-OF-THE-ART]. 2649 23

Intrahepatic cholestasis of pregnancy (ICP) affects 1/140 UK pregnancies; with pruritus, hepatic impairment and elevated serum bile acids. Severe disease is complicated by spontaneous preterm delivery and stillbirth. Previous studies have reported mutations in hepatocellular transporters (ABCB4, ABCB11). High throughput sequencing in 147 patients was performed in the transporters ABCB4, ABCB11, ATP8B1, ABCC2 and tight junction protein 2 (TJP2). Twenty-six potentially damaging variants were identified with the following predicted protein changes: Twelve ABCB4 mutations - Arg47Gln, Met113Val, Glu161Gly, Thr175Ala, Glu528Glyfs*6, Arg590Gln, Ala601Ser, Glu884Ter, Gly722Ala, Tyr775Met (x2), Trp854Ter. Four potential ABCB11 mutations - Glu297Gly (x3) and a donor splice site mutation (intron 19). Five potential ATP8B1 mutations - Asn45Thr (x3), and two others, Glu114Gln and Lys203Glu. Two ABCC2 mutations - Glu1352Ala and a duplication (exons 24 and 25). Three potential mutations were identified in TJP2; Thr62Met (x2) and Thr626Ser. No patient harboured more than one mutation. All were heterozygous. An additional 545 cases were screened for the potential recurrent mutations of ATP8B1 (Asn45Thr) and TJP2 (Thr62Met) identifying three further occurrences of Asn45Thr. This study has expanded known mutations in ABCB4 and ABCB11 and identified roles in ICP for mutations in ATP8B1 and ABCC2. Possible novel mutations in TJP2 were also discovered.
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PMID:An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy. 2892 28