钠离子牛磺胆酸共转运多肽缺陷病及其对母胎影响的研究进展

doi:10.12280/gjfckx.20230675

国际妇产科学杂志 ›› 2023, Vol. 50 ›› Issue (6): 684-688.doi: 10.12280/gjfckx.20230675

• 产科生理及产科疾病:综述 • 上一篇下一篇

钠离子牛磺胆酸共转运多肽缺陷病及其对母胎影响的研究进展

赵欢, 余晓明, 白晓霞^△()

322000 浙江省义乌市，浙江大学医学院附属第四医院妇产科（赵欢）; 浙江大学医学院附属妇产科医院产科（余晓明，白晓霞）

收稿日期:2023-08-31 出版日期:2023-12-15 发布日期:2023-12-13
通讯作者: 白晓霞 E-mail:baixiaoxia@zju.edu.cn
作者简介:^△审校者
基金资助:
国家中医药管理局科技司-浙江省中医药管理局共建科技计划重点项目(GZY-ZJ-KJ-23082);浙江省卫生创新人才项目(A0466)

Research Progress on Sodium-Taurocholate Cotransporting Polypeptide Deficiency Disease and Its Impact on Mother and Fetus

ZHAO Huan, YU Xiao-ming, BAI Xiao-xia()

Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, Zhejiang Province, China (ZHAO Huan); Department of Obstetrics, Women′s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China (YU Xiao-ming, BAI Xiao-xia)

Received:2023-08-31 Published:2023-12-15 Online:2023-12-13
Contact: BAI Xiao-xia E-mail:baixiaoxia@zju.edu.cn

摘要/Abstract

摘要：

钠离子牛磺胆酸共转运多肽（sodium-taurocholate cotransporting polypeptide，NTCP）缺陷病是一种溶质载体家族10成员1（solute carrier family 10 member 1，SLC10A1）双等位基因突变引起的胆汁酸代谢障碍性疾病，分布具有区域和种族差异，其中SLC10A1 c.800C>T (p.Ser267Phe)是我国的高频突变。NTCP缺陷病患儿主要表现为病理性黄疸，少部分有生长、运动和神经系统发育迟缓的表现，成年患者临床症状和体征不明显，生化检查提示血清总胆汁酸水平升高、部分伴有转氨酶和25-羟维生素D₃水平降低。NTCP缺陷病性高胆汁酸血症需与乙型肝炎病毒感染、丁型肝炎病毒感染、自身免疫性肝炎及妊娠期肝内胆汁淤积症等鉴别，妊娠合并NTCP缺陷病性高胆汁酸血症对母胎的影响迄今少有相关报道。综述NTCP缺陷病的分子遗传机制、临床表现、实验室检查、诊断、治疗及其对母胎的影响，为该病患者的明确诊断和正确干预提供依据。

关键词: 遗传变异, 溶质载体蛋白质类, 胆汁淤积, 肝内, 钠离子牛磺胆酸共转运多肽缺陷病, SLC10A1基因

Abstract:

Sodium-taurocholate cotransporting polypeptide (NTCP) deficiency disease is a bile acid metabolic disease caused by biallelic mutations in solute carrier family 10 member 1 (SLC10A1), with regional and racial differences in distribution, and SLC10A1 c.800C>T (p.Ser267Phe) is a high-frequency mutation in China. Children with NTCP deficiency disease are mainly manifested as pathological jaundice and a small proportion could have delayed growth, motor and neurological development. While in adults, clinical symptoms and signs are not obvious, biochemical tests indicate elevated serum total bile acid levels, and some are accompanied by decreased levels of transaminase and 25-hydroxyvitamin D₃. The high concentration of serum bile acids of NTCP deficiency needs to be distinguished from hepatitis B and D virus infection, autoimmune hepatitis and intrahepatic cholestasis of pregnancy. There have been few reports about the effects of pregnancy combined with the high concentration of serum bile acids caused by NTCP deficiency on the mother and fetus. The molecular genetic mechanism, clinical manifestations, laboratory tests, diagnosis, treatments and its impact on the mother and fetus of NTCP deficiency disease were reviewed to provide a basis for the clear diagnosis and correct intervention of patients with this disease.

Key words: Genetic variation, Solute carrier proteins, Cholestasis, intrahepatic, Sodium-taurocholate cotransporting polypeptide deficiency disease, SLC10A1 gene

赵欢, 余晓明, 白晓霞. 钠离子牛磺胆酸共转运多肽缺陷病及其对母胎影响的研究进展[J]. 国际妇产科学杂志, 2023, 50(6): 684-688.

ZHAO Huan, YU Xiao-ming, BAI Xiao-xia. Research Progress on Sodium-Taurocholate Cotransporting Polypeptide Deficiency Disease and Its Impact on Mother and Fetus[J]. Journal of International Obstetrics and Gynecology, 2023, 50(6): 684-688.

参考文献 28

[1]	Wettengel JM, Burwitz BJ. Innovative HBV Animal Models Based on the Entry Receptor NTCP[J]. Viruses, 2020, 12(8):828. doi: 10.3390/v12080828.
[2]	Santos Silva E, Rocha S, Candeias Ramos R, et al. Bile acids profile and redox status in healthy infants[J]. Pediatr Res, 2023, 93(7):1856-1864. doi: 10.1038/s41390-022-02350-y.
[3]	Liu H, Irobalieva RN, Bang-Sørensen R, et al. Structure of human NTCP reveals the basis of recognition and sodium-driven transport of bile salts into the liver[J]. Cell Res, 2022, 32(8):773-776. doi: 10.1038/s41422-022-00680-4. pmid: 35726088
[4]	Goutam K, Ielasi FS, Pardon E, et al. Structural basis of sodium-dependent bile salt uptake into the liver[J]. Nature, 2022, 606(7916):1015-1020. doi: 10.1038/s41586-022-04723-z.
[5]	Park JH, Iwamoto M, Yun JH, et al. Structural insights into the HBV receptor and bile acid transporter NTCP[J]. Nature, 2022, 606(7916):1027-1031. doi: 10.1038/s41586-022-04857-0.
[6]	Asami J, Kimura KT, Fujita-Fujiharu Y, et al. Structure of the bile acid transporter and HBV receptor NTCP[J]. Nature, 2022, 606(7916):1021-1026. doi: 10.1038/s41586-022-04845-4.
[7]	Qi X, Li W. Unlocking the secrets to human NTCP structure[J]. Innovation(Camb), 2022, 3(5):100294. doi: 10.1016/j.xinn.2022.100294.
[8]	Saran C, Ho H, Honkakoski P, et al. Effect of mTOR inhibitors on sodium taurocholate cotransporting polypeptide (NTCP) function in vitro[J]. Front Pharmacol, 2023, 14:1147495. doi: 10.3389/fphar.2023.1147495.
[9]	Zhang Q, He Z, Liu Z, et al. Integrated plasma and liver gas chromatography mass spectrometry and liquid chromatography mass spectrometry metabolomics to reveal physiological functions of sodium taurocholate cotransporting polypeptide (NTCP) with an Ntcp knockout mouse model[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2021, 1165:122531. doi: 10.1016/j.jchromb.2021.122531.
[10]	Mao F, Wang MX, Hou X, et al. NTCP Deficiency Causes Gallbladder Abnormalities in Mice and Human Beings[J]. Cell Mol Gastroenterol Hepatol, 2021, 11(3):831-839. doi: 10.1016/j.jcmgh.2020.09.001. pmid: 32919083
[11]	Yang F, Xu W, Wu L, et al. NTCP Deficiency Affects the Levels of Circulating Bile Acids and Induces Osteoporosis[J]. Front Endocrinol(Lausanne), 2022, 13:898750. doi: 10.3389/fendo.2022.898750.
[12]	Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus[J]. eLife, 2012, 1:e00049. doi:10.7554/eLife.00049.
[13]	Urban S, Neumann-Haefelin C, Lampertico P. Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease[J]. Gut, 2021, 70(9):1782-1794. doi: 10.1136/gutjnl-2020-323888. pmid: 34103404
[14]	Salhab A, Amer J, Lu Y, et al. Sodium⁺/taurocholate cotransporting polypeptide as target therapy for liver fibrosis[J]. Gut, 2022, 71(7):1373-1385. doi: 10.1136/gutjnl-2020-323345.
[15]	Li H, Chen R, Lin GZ, et al. Molecular Epidemiology of Na⁺-Taurocholate Cotransporting Polypeptide Deficiency in Guangdong Province, China: A Pilot Study by Screening for Four Prevalent Variants of the Causative Gene SLC10A1[J]. Front Genet, 2022, 13:874379. doi: 10.3389/fgene.2022.874379.
[16]	Song R, Hu M, Qin X, et al. The Roles of Lipid Metabolism in the Pathogenesis of Chronic Diseases in the Elderly[J]. Nutrients, 2023, 15(15):3433. doi: 10.3390/nu15153433.
[17]	Deng LJ, Ouyang WX, Liu R, et al. Clinical characterization of NTCP deficiency in paediatric patients : A case-control study based on SLC10A1 genotyping analysis[J]. Liver Int, 2021, 41(11):2720-2728. doi: 10.1111/liv.15031. pmid: 34369070
[18]	Schneider AL, Köhler H, Röthlisberger B, et al. Sodium taurocholate co-transporting polypeptide deficiency[J]. Clin Res Hepatol Gastroenterol, 2022, 46(3):101824. doi: 10.1016/j.clinre.2021.101824.
[19]	Liu R, Chen C, Xia X, et al. Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine[J]. Sci Rep, 2017, 7(1):9214. doi: 10.1038/s41598-017-07012-2.
[20]	林桂枝. 广东人群钠牛磺胆酸共转运多肽缺陷病分子流行病学调查[D]. 广州: 暨南大学, 2020.
[21]	Vaz FM, Paulusma CC, Huidekoper H, et al. Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: conjugated hypercholanemia without a clear clinical phenotype[J]. Hepatology, 2015, 61(1):260-267. doi: 10.1002/hep.27240. pmid: 24867799
[22]	Deng M, Mao M, Guo L, et al. Clinical and molecular study of a pediatric patient with sodium taurocholate cotransporting polypeptide deficiency[J]. Exp Ther Med, 2016, 12(5):3294-3300. doi: 10.3892/etm.2016.3752. pmid: 27882152
[23]	Liu HY, Li M, Li Q. De novo mutation loci and clinical analysis in a child with sodium taurocholate cotransport polypeptide deficiency: A case report[J]. World J Clin Cases, 2021, 9(36):11487-11494. doi: 10.12998/wjcc.v9.i36.11487.
[24]	王彩红, 卓志强, 黄冰清, 等. Citrin缺陷病6例临床特征及基因型特点[J]. 肝脏, 2020, 25(11):1223-1226,1240. doi: 10.3969/j.issn.1008-1704.2020.11.027.
[25]	纪培林, 宋元宗. 同一患儿罹患3种遗传性肝病报道[J]. 河南医学研究, 2022, 31(1):184-187. doi: 10.3969/j.issn.1004-437X.2022.01.050.
[26]	Zou TT, Zhu Y, Wan CM, et al. Clinical features of sodium-taurocholate cotransporting polypeptide deficiency in pediatric patients: case series and literature review[J]. Transl Pediatr, 2021, 10(4):1045-1054. doi: 10.21037/tp-20-360.
[27]	Van Herpe F, Waterham HR, Adams CJ, et al. NTCP deficiency and persistently raised bile salts: an adult case[J]. J Inherit Metab Dis, 2017, 40(3):313-315. doi: 10.1007/s10545-017-0031-9. pmid: 28283843
[28]	Chen R, Deng M, Rauf YM, et al. Intrahepatic Cholestasis of Pregnancy as a Clinical Manifestation of Sodium-Taurocholate Cotransporting Polypeptide Deficiency[J]. Tohoku J Exp Med, 2019, 248(1):57-61. doi: 10.1620/tjem.248.57. pmid: 31142693

钠离子牛磺胆酸共转运多肽缺陷病及其对母胎影响的研究进展

Research Progress on Sodium-Taurocholate Cotransporting Polypeptide Deficiency Disease and Its Impact on Mother and Fetus

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