法尼酯衍生物X受体基因多态性与代谢性疾病的相关性

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (10): 1180-1188.

法尼酯衍生物X受体基因多态性与代谢性疾病的相关性

徐千¹，李玲¹，魏婉慧¹，赵慧佳¹，时玉颖¹，乐江²，王彦峰¹，叶啟发^1,3

¹武汉大学中南医院，武汉大学肝胆疾病研究院，武汉大学移植医学中心，移植医学技术湖北省重点实验室，武汉 430071，湖北；²武汉大学基础医学院药理教研室，武汉 430071，湖北；³中南大学湘雅三医院，卫生部移植医学工程技术研究中心，长沙 410013，湖南

收稿日期:2017-03-17 修回日期:2017-08-25 出版日期:2017-10-26 发布日期:2017-11-13
通讯作者: 叶啟发，男，主任医师，教授，研究方向：肝胆外科、器官移植。 Tel：027-67812988 E-mail：yqf_china@163.com
作者简介:徐千，男，本科，研究方向：基因多态性在器官移植中的应用。 Tel：13659887549 E-mail：3059258427@qq.com
基金资助:
湖北省自然科学基金创新群体（2015CFA018）；湖北省卫计委药护技和管理专项（WJ2017H0024）；武汉大学中南医院药护技和管理专项（xcpy20160062）

Farnesoid X receptor gene polymorphisms and metabolic disease

XU Qian ¹, LI Ling ¹, WEI Wanhui¹, ZHAO Huijia ¹, SHI Yuying ¹, YUE Jiang² , WANG Yanfeng ¹, YE Qifa ^1,3

¹Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan 430071, Hubei, China; ²Department of Pharmacology, School of Basic Medicine, Wuhan University, Wuhan 430071, Hubei, China; ³ The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha 410013, Hunan, China

Received:2017-03-17 Revised:2017-08-25 Online:2017-10-26 Published:2017-11-13

摘要/Abstract

摘要：

法尼酯X受体(farnesoid X receptor，FXR)，是由配体激活、维持机体稳态的一种转录因子。作为一种多功能核受体，入核后与视黄醛衍生物受体 (retinoid X receptor, RXR) 形成异质二聚体，与反向重复序列-1（inverted repeat-1, IR1）结合调节靶基因表达。其靶基因涉及脂肪酸、胆汁酸、葡萄糖代谢，进而决定了FXR与胆汁淤积、糖尿病、高血压、脂质紊乱等代谢性疾病的密切联系。研究表明，多个FXR基因多态性位点与代谢性疾病的发生密切相关，如rs56163822与糖代谢紊乱相关，rs35724 和rs10860603会影响身体质量指数（body mass index,BMI）。本文拟就近年来FXR参与代谢途径及其基因多态性与代谢性疾病的相关性作一综述，为代谢性疾病的发生几率评估及提前干预提供新思路。

关键词: 法尼酯X受体, 基因多态性, 代谢性疾病

Abstract:

Farnesoid X receptor (FXR)is a ligand-activated transcription factor that maintains homeostasis. In the nucleus, FXR forms a heterodimer with RXR and binds to inverted repeat elements separated by one nucleotide (IR-1) to regulate the expression of target genes. Highly expressed in the human liver, intestine, kidneys and adrenals, FXR is an important regulator of bile acid, lipid and glucose metabolism. This makes FXR a potential therapeutic target in metabolic disease. What's more, FXR SNPs (single-nucleotide polymorphisms) are proved to be associated with cholelithiasis, glucose homeostasis, intrahepatic cholestasis and obesity. This review focuses on the metabolic pathway and the gene polymorphism of FXR, which can bring the results of early identification and prevention of some metabolic diseases.

Key words: farnesoid X receptor, gene polymorphism, metabolic disease

中图分类号:

R589

徐千，李玲，魏婉慧，赵慧佳，时玉颖，乐江，王彦峰，叶啟发. 法尼酯衍生物X受体基因多态性与代谢性疾病的相关性[J]. 中国临床药理学与治疗学, 2017, 22(10): 1180-1188.

XU Qian, LI Ling, WEI Wanhui, ZHAO Huijia, SHI Yuying, YUE Jiang, WANG Yanfeng, YE Qifa. Farnesoid X receptor gene polymorphisms and metabolic disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(10): 1180-1188.

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