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Feasibility of urinary microRNA profiling detection in intrahepatic cholestasis of pregnancy and its potential as a non-invasive biomarker.

ABSTRACT: Intrahepatic cholestasis of pregnancy (ICP), a pregnancy-related liver disease, leads to complications for both mother and fetus. Circulating microRNAs (miRNAs) have emerged as candidate biomarkers for many diseases. So far, the circulating miRNAs profiling of ICP has not been investigated. To assess the urinary miRNAs as non-invasive biomarkers for ICP, a differential miRNA profiling was initially analyzed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay in urinary samples from a screening set including 10 ICP and 10 healthy pregnancies. The selected candidate miRNAs were then validated by a validation set with 40 ICP and 50 healthy pregnancies using individual qRT-PCR assay. Compared with the expression in urine of healthy pregnant women, the expression levels of hsa-miR-151-3p and hsa-miR-300 were significantly down-regulated, whereas hsa-miR-671-3p and hsa-miR-369-5p were significantly up-regulated in urine from ICP patients (p?

SUBMITTER: Ma L

PROVIDER: S-EPMC4989235 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Feasibility of urinary microRNA profiling detection in intrahepatic cholestasis of pregnancy and its potential as a non-invasive biomarker.

Ma Li L Zhang Xiao-Qing XQ Zhou Da-Xue DX Cui Yue Y Deng Lin-Lin LL Yang Ting T Shao Yong Y Ding Min M

Scientific reports 20160818

Intrahepatic cholestasis of pregnancy (ICP), a pregnancy-related liver disease, leads to complications for both mother and fetus. Circulating microRNAs (miRNAs) have emerged as candidate biomarkers for many diseases. So far, the circulating miRNAs profiling of ICP has not been investigated. To assess the urinary miRNAs as non-invasive biomarkers for ICP, a differential miRNA profiling was initially analyzed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assa ...[more]

PMID: 27534581

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Project description:The ABCB4 gene encodes multidrug resistance protein 3(MDR3), which is a phosphatidylcholine(PC) transfer enzyme that transfers lecithin from the inner part of the phospholipid bilayer to the extracellular bile. The occurrence of intrahepatic cholestasis of pregnancy(ICP) is closely related to ABCB4 variants, but there is limited research on this topic in southern Anhui, China. We sequenced ABCB4 in pregnant women with ICP and healthy pregnant women to explore the relationship. A total of 30 patients diagnosed with ICP were selected as the study objects and 90 healthy pregnant women were selected as the control group. DNA was extracted from peripheral blood of ICP patients and healthy pregnant women, 27 exons were sequencing by Sanger sequencing. Polymerase chain reaction (PCR) was used to amplify those exons. PolyPhen2, Mutation Taster, Provean, SIFT and Mutpred2 were used to predict protein structure, and Pymol software was used to predict the impact of missense variant c.1954 A > G(p.Arg652Gly) on proteins. Four exonic variants of ABCB4 gene were detected in ICP patients and healthy pregnant women, including synonymous variants c.175 C > T, c.504 C > T,c.711 A > T and missense variant c.1954 A > G(p.Arg652Gly). The incidence of the missense variant c.1954 A > G(p.Arg652Gly) was 6/90 in healthy pregnant womenand 8/30 in ICP patients.In healthy pregnant women with the missense variant c.1954 A > G(p.Arg652Gly), no other exonic variants were found. In ICP patients with missense variant c.1954 A > G(p.Arg652Gly), other exonic variants were found. PolyPhen2, Mutation Taster, Provean, SIFT and Mutpred2 were used to predict that the four exonic variants were benign, while Pymol was used to showed that the missense variant was located in the linker region of MDR3 and had a slight impact on protein function. Among ICP patients with missense variant c.1954 A > G(p.Arg652Gly), patients with three exonic variants(c.504 C > T, c.711 A > T, c.1954 A > G) had higher γ-GT, TBA, ALT and AST than those with two exonic variants. ABCB4 missense variant c.1954 A > G(p.Arg652Gly) requires the combination of other variants(c.175 C > T, c.504 C > T,c.711 A > T) to cause ICP symptoms, and when combined with other variants, it has a superimposed effect.

Dataset Information

Feasibility of urinary microRNA profiling detection in intrahepatic cholestasis of pregnancy and its potential as a non-invasive biomarker.

Publications

Feasibility of urinary microRNA profiling detection in intrahepatic cholestasis of pregnancy and its potential as a non-invasive biomarker.

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