ABCB4变异与妊娠肝内胆汁淤积的关系

IF 3.9 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-01-26 DOI:10.1038/s41598-025-87909-5

Dekun Zhang, Yuhong Li, Shufeng He, Jing Shu, Tiechen Li, Qing Sun

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引用次数: 0

摘要

ABCB4基因编码多药耐药蛋白3(MDR3)，这是一种磷脂酰胆碱（PC）转移酶，将卵磷脂从磷脂双分子层的内部转移到细胞外胆汁。妊娠肝内胆汁淤积症（ICP）的发生与ABCB4变异密切相关，但在皖南地区的相关研究有限。我们对ICP孕妇和健康孕妇的ABCB4进行了测序，以探讨两者之间的关系。选取30例诊断为ICP的患者作为研究对象，90例健康孕妇作为对照组。从ICP患者和健康孕妇外周血中提取DNA，采用Sanger测序法对27个外显子进行测序。用聚合酶链反应（PCR）扩增这些外显子。用PolyPhen2、Mutation Taster、Provean、SIFT和Mutpred2预测蛋白结构，用Pymol软件预测错义变异c.1954的影响A > G（p.Arg652Gly）在蛋白质上。在ICP患者和健康孕妇中检测到ABCB4基因的4个外显子变体，包括同义变体c.175C b> T, C 504C b> T, C 711b> T和错义变体c.1954A b> G（p.Arg652Gly）。错义变异的发病率c.1954健康孕妇的b> G（p.a g652gly）为6/90，ICP患者为8/30。携带错义变异c.1954的健康孕妇A >g (p.a g652gly)，未发现其他外显子变异。错义变异的ICP患者c.1954发现了一个>g (p.a g652gly)，其他外显子变异。PolyPhen2、Mutation Taster、Provean、SIFT和Mutpred2预测4个外显子变异为良性，Pymol预测错义变异位于MDR3的连接区，对蛋白功能有轻微影响。错义变异的ICP患者c.1954A >g (p.a g652gly)，患者有3个外显子变异（c.a 504）C b> T, C 711A bbbbt, c.1954A > G)的γ-GT、TBA、ALT和AST均高于2个外显子变体。ABCB4错义变体c.1954b> G（p.a g652gly）需要其他变体（c.p 175）的组合C b> T, C 504C b> T, C 711一个bbb10t)引起ICP症状，当与其他变异合并时，它有叠加效应。

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Association between ABCB4 variants and intrahepatic cholestasis of pregnancy.

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Association between ABCB4 variants and intrahepatic cholestasis of pregnancy.

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.

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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