人细胞色素P450 1A2的发育变化及基因多态性的临床意义  

Clinical Significance of Human Cytochrome P450 1A2 Ontogeny and Its Gene Polymorphism

作　　者：高向波[1,2] 江周虹 王玉梅[1] 余露山[2] 倪韶青[1] GAO Xiang-bo;JIANG Zhou-hong;WANG Yu-mei;YU Lu-shan;NI Shao-qing(Children′s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China;College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China)

机构地区：[1]浙江大学医学院附属儿童医院,杭州310052 [2]浙江大学药学院,杭州310058

出　　处：《中国药学杂志》2019年第10期766-772,共7页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(81573516,81273607)

摘　　要：综述发育过程中细胞色素P450 1A2(cytochrome P450 1A2,CYP1A2)代谢酶的变化及基因多态性对临床用药的影响。通过查阅国内外相关文献,进行分析、归纳和总结。CYP1A2是人类药物代谢酶重要的亚家族之一,参与临床上约8%~10%的药物代谢,具有重要的药理学和毒理学意义。不同发育阶段CYP1A2酶的表达和活性存在差异,其探针底物咖啡因表现出不同的清除率和消除半衰期。基因多态性会引起酶活性的差异,研究较多的且存在潜在预测价值的CYP1A2*1C和CYP1A2*1F基因多态性可引起酶活性变化,在成年人临床用药中时常表现出较显著的影响。关于早产儿、婴幼儿、儿童中CYP1A2基因多态性与酶活性的相关性及对药物影响的研究报道非常有限。基因多态性与发育因素的相互作用对不同发育阶段CYP1A2活性的影响尚未知。深入细化研究发育过程中CYP1A2的变化规律及基因多态性对药物代谢的影响,对于提高儿童临床用药的安全性和有效性是非常必要的。The change of human cytochrome P450 1A2 ontogeny and the effect of its gene polymorphism on clinical medication were reviewed. The relevant literatures from various databases were searched, collected, analyzed and summarized. CYP1A2 is one of the major subfamilies in human liver enzyme. It is involved in metabolism of about 8%-10% of drugs in clinic, which has important pharmacological and toxicological implications.The expression and activity of CYP1A2 enzymes were different during development, which had a significant effect on clinical medication in human. Studies can see clearance rates and elimination half-lives differences by using caffeine as a probe substrate.Gene polymorphisms cause activity differences of CYP1A2. Gene polymorphisms of CYP1A2*1C and CYP1A2*1F, have been extensively studied show significant effects on clinical medication in adults.There are very few studies on medication between CYP1A2 gene polymorphism and enzyme activity in premature infants, infants and children. The effect of CYP1A2 enzyme activity is unknown between gene polymorphism and ontogeny interaction during human development.It is very necessary to further study the ontogeny changes of CYP1A2 and its gene polymorphism on drug metabolism for improving the safety and efficacy medication in children.

关 键 词：细胞色素P450 1A2 个体发育 基因多态性 临床用药 儿童 

分 类 号：R969.3[医药卫生—药理学]