P450酶和转运体的DNA甲基化调控:提示药物反应的个体差异

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (11): 1294-1299.

P450酶和转运体的DNA甲基化调控:提示药物反应的个体差异

杨杰¹, 谭洁², 邹建军², 周俊山¹, 谢海棠³

¹南京医科大学附属南京第一医院神经内科, ²临床药理实验室,南京 210006,江苏;
³安徽省药物临床评价中心,芜湖 241001,安徽

收稿日期:2010-10-10 修回日期:2010-11-10 出版日期:2010-11-26 发布日期:2020-09-16
通讯作者: 邹建军,男,博士,从事基因多态性和临床个体化给药研究。E-mail: zoujianjun100@126.com
作者简介:杨杰,男,博士,从事脑血管疾病的临床诊治和遗传学研究。Tel: 18951670108
基金资助:
国家自然科学基金项目(30901830);江苏省高校自然科学研究项目(10KJB320001);南京市医学科技发展项目(QYK10137)

DNA methylation and the regulation of P450 enzymes and transporters:implications for interindividual variability in response to drugs

YANG Jie¹, TAN Jie² , ZOU Jian-jun¹, ZHOU Jun-shan¹, XIE Hai-tang³

¹Department of Neurology, Nanjing First Hospital of Nanjing Medical University, ²Department of Clinical Pharmacology, Nanjing 210006, Jiangsu, China;
³Center for Drug Clinical Evaluation of Anhui Province, Wuhu 241001, Anhui, China

Received:2010-10-10 Revised:2010-11-10 Online:2010-11-26 Published:2020-09-16

摘要/Abstract

摘要： 细胞色素P450酶和转运体的基因多态性已被公认是导致临床上药物反应个体差异的重要原因,但个体间某些代谢酶、转运体的基因型和表型不一致的现象不能完全用基因多态性来解释。表观遗传药理学从表观遗传学的角度来研究遗传因素与药物治疗的关系,为药物反应的个体差异提供了新的解释。P450酶和转运体都受表观遗传因素控制。最常见表观遗传调控机制是DNA甲基化,它不会改变基因的遗传代码,而影响基因的表达。由于它对基因组序列的维护,DNA甲基化可用来解释某些基因多态性与表型的不一致现象。本综述总结了DNA甲基化表观遗传调控机制对P450酶和转运体的基因表达影响的最新进展。

关键词: 细胞色素P450, 转运体, DNA甲基化, 个体差异

Abstract: Gene polymorphisms of Cytochrome P450 enzymes and transporters have been recognized as causes of interindividual variability in response to drugs. But some inconsistencies of the gene polymorphism and the phenotype of certain metabolic enzymes, transporter genotype can not be completely explained on the basis of genetic polymorphisms.Parmacoepigeneties is to study the relationship between genetic factors and drug therapy from the perspective of epigenetics and offer new explanation for interindividual variations in drug response.P450 enzymes and transporters are subject to epigenetic control. The most common epigenetic mechanism is DNA methylation, which does not change the genetic code, but might affect gene expression.Since the maintenance of its genome sequence, DNA methylation can be used to explain some inconsistencies of the gene polymorphism and the phenotype. In this overview,we summarize the newest advancement of the regulation of DNA methylation in epigenetic mechanisms of P450 enzymes and transporter gene expression.

Key words: Cytochrome P450, Transporters, DNA methylation, Interindividual Variability

中图分类号:

R968

杨杰, 谭洁, 邹建军, 周俊山, 谢海棠. P450酶和转运体的DNA甲基化调控:提示药物反应的个体差异[J]. 中国临床药理学与治疗学, 2010, 15(11): 1294-1299.

YANG Jie, TAN Jie , ZOU Jian-jun, ZHOU Jun-shan, XIE Hai-tang. DNA methylation and the regulation of P450 enzymes and transporters:implications for interindividual variability in response to drugs[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(11): 1294-1299.

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