CYP2R1的遗传多态性及其个体化治疗应用

doi:10.12092/j.issn.1009-2501.2019.09.014

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (9): 1053-1059.doi: 10.12092/j.issn.1009-2501.2019.09.014

CYP2R1的遗传多态性及其个体化治疗应用

李玲^1,2，赵慧佳¹，陈彬尧¹，刘晓红¹，孙功鹏¹，郝卓文¹，范志鹏¹，乐江²，吴建国³，叶啟发^1,4

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武汉大学生命科学学院，病毒学国家重点实验室，武汉 430071，湖北；⁴中南大学湘雅三医院，卫生部移植医学工程技术研究中心，湖南 410013，长沙

收稿日期:2018-09-21 修回日期:2019-01-09 出版日期:2019-09-26 发布日期:2019-09-26
通讯作者: 叶啟发，男，教授，主任医师，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:李玲，女，博士研究生在读，主管药师，研究方向：器官移植术后并发症的个体化治疗。 Tel:15387041070 E-mail: wh001019@whu.edu.cn
基金资助:
2016年湖北省技术创新专项（2016ACA155）；病毒学国家重点实验室开放研究基金资助项目（2018KF005）；湖北省卫计委药护技和管理专项（WJ2017H0024）

Relevance of CYP2R1 genetic polymorphism and individual therapy

LI Ling ^1,2, ZHAO Huijia¹, CHEN Binyao ¹, LIU Xiaohong ¹, SUN Gongpeng ¹, HAO Zhuowen ¹, FAN Zhipeng¹, YUE Jiang², WU Jianguo³, YE Qifa ^1,4

¹ Zhongnan 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; ² Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, Hubei, China; ³ College of Life Sciences of Wuhan University, State Key Laboratory of Virology, Wuhan 430071, Hubei, China; ⁴The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha 410013, Hunan, China

Received:2018-09-21 Revised:2019-01-09 Online:2019-09-26 Published:2019-09-26

摘要/Abstract

摘要：

CYP2R1是细胞色素P450家族2亚家族的成员，作为维生素D的25-羟化酶，负责将维生素D羟基化为25-羟基维生素D（25-OH-D），影响活性激素1,25(OH)2D的生成。CYP2R1突变会引发维生素D依赖型佝偻病1B型，且CYP2R1的多态性与25-OH-D水平显著相关，尤其是rs10741657。CYP2R1基因多态性会影响其蛋白表达水平和酶活性，对其催化的代谢过程产生显著影响。CYP2R1通过调节基因功能，从而调节免疫反应，影响1型糖尿病的发病风险。其多态性与多种癌症的风险相关，包括乳腺癌，前列腺癌和结肠直肠癌。研究 CYP2R1基因多态性有利于深入了解代谢途径的改变在相关疾病发生发展中的作用，加深对癌症、佝偻病、1型糖尿病等疾病的认识，促进从基因层面检测和评估相关疾病的发生风险。本文拟就近五年CYP2R1参与的代谢途径和基因多态性对其影响的研究进展作一综述。

关键词: CYP2R1, 遗传多态性, 维生素D缺乏, 1型糖尿病, 癌症

Abstract:

CYP2R1 is a member of the cytochrome P450 family 2 subfamily. As a 25-hydroxylase of vitamin D, it is responsible for the hydroxylation of vitamin D to 25-hydroxyvitamin D (25-OH-D), affecting the production of active hormone 1,25(OH)2D. The CYP2R1 mutation triggers a vitamin D-dependent rickets type 1B. The polymorphism of CYP2R1 is significantly correlated with the level of 25-OH-D, especially rs10741657. The CYP2R1 gene polymorphism affects its protein expression level and enzyme activity, and has a significant impact on the metabolic processes that it catalyzes. CYP2R1 regulates the immune response by regulating gene function and affects the risk of type 1 diabetes. Its polymorphism is associated with a variety of cancer risks, including breast cancer, prostate cancer, and colorectal cancer. Studying the CYP2R1 gene polymorphism is helpful for understanding the role of metabolic pathway changes in the development of related diseases, deepening the understanding of diseases such as cancer, rickets and type 1 diabetes, and promoting the detection and assessment of the risk of related diseases from the genetic level. This article reviews the research progress of metabolic pathways and gene polymorphisms involved in CYP2R1 in recent five years.

Key words: CYP2R1, genetic polymorphism, vitamin D deficiency, type 1diabetes, cancer

中图分类号:

R966
R587.1

李玲，赵慧佳，陈彬尧，刘晓红，孙功鹏，郝卓文，范志鹏，乐江，吴建国，叶啟发. CYP2R1的遗传多态性及其个体化治疗应用[J]. 中国临床药理学与治疗学, 2019, 24(9): 1053-1059.

LI Ling, ZHAO Huijia, CHEN Binyao, LIU Xiaohong, SUN Gongpeng, HAO Zhuowen, FAN Zhipeng, YUE Jiang, WU Jianguo, YE Qifa. Relevance of CYP2R1 genetic polymorphism and individual therapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(9): 1053-1059.

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CYP2R1的遗传多态性及其个体化治疗应用

Relevance of CYP2R1 genetic polymorphism and individual therapy

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