In vitro functional analysis of 24 novel CYP2C19 variants recently found in the Chinese Han population

doi:10.3109/00498254.2015.1028512

科研成果详情

题名	In vitro functional analysis of 24 novel CYP2C19 variants recently found in the Chinese Han population
作者	Dai, Da-Peng 1; Hu, Li-Ming 2; Geng, Pei-Wu 3; Wang, Shuang-Hu 3; Cai, Jie 1,4; Hu, Guo-Xin4; Cai, Jian-Ping 1
发表日期	2015-12-31
发表期刊	XENOBIOTICA 影响因子和分区
语种	英语
原始文献类型	Article
关键词	CYP2C19 drug metabolism omeprazole polymorphisms S-mephenytoin
其他关键词	HUMAN CYTOCHROME-P450 ENZYMES ; ALLELIC VARIANTS ; CLOPIDOGREL RESISTANCE ; GENETIC POLYMORPHISMS ; METABOLISM ; PHARMACOKINETICS ; 2C19 ; FREQUENCIES ; OMEPRAZOLE ; JAPANESE
摘要	1. CYP2C19 is a highly polymorphic enzyme responsible for the metabolism of a wide range of clinical drugs. Alterations to the CYP2C19 gene contribute to the variability of CYP2C19 enzyme activity, which causes pharmacokinetics and drug efficacies to vary and adverse drug reactions to occur in different persons. Recently, we identified 24 novel CYP2C19 allelic variants in the Chinese Han population. The purpose of present study is to assess the impact of these newly found nucleotide mutations on the enzymatic activity of the CYP2C19 protein. 2. Dual-expression vectors were constructed and transiently transfected into 293FT cells. Forty-eight hours after transfection, cells were re-suspended and incubated with two typical probe substrates, omeprazole and S-mephenytoin, to determine the activities of each variant relative to the wild-type protein. 3. Immunoblotting results showed that the protein expression levels of the CYP2C19 variants were diverse. Enzymatic ability analysis showed that the variant 35FS exhibited no functional activity, and most of the other variants showed significantly decreased metabolic activities toward both omeprazole and S-mephenytoin compared with wild-type. 4. These findings greatly enrich the knowledge of biological effects of these newly found CYP2C19 mutations and aid the application of this knowledge to future individualized drug therapy in clinic.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31371280]; National Health and Family Planning Commission of the People's Republic of China [201302008]
出版者	TAYLOR & FRANCIS LTD
出版地	ABINGDON
ISSN	0049-8254
EISSN	1366-5928
卷号	45 期号:11 页码:1030-1035
DOI	10.3109/00498254.2015.1028512
页数	6
WOS类目	Pharmacology & Pharmacy ; Toxicology
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
WOS记录号	WOS:000369949100010
收录类别	SCIE ; SCOPUS
URL	查看原文
PubMed ID	26153442
SCOPUSEID	2-s2.0-84942296858
通讯作者地址	[Hu, Guo-Xin]Department of Pharmacology,School of Pharmacy,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
Scopus学科分类	Biochemistry;Toxicology;Pharmacology;Health, Toxicology and Mutagenesis
引用统计	被引频次：12[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/7018
专题	药学院（分析测试中心）药学院（分析测试中心）_临床药学与药理系
通讯作者	Hu, Guo-Xin
作者单位	1.Key Laboratory of Geriatrics,Beijing Hospital,Beijing Institute of Geriatrics,Beijing,100730,China; 2.Department of Pharmacy,First People's Hospital of Wenling,Wenling, Zhejiang,China; 3.Laboratory of Clinical Pharmacy,Peoples Hospital of Lishui,Lishui, Zhejiang,China; 4.Department of Pharmacology,School of Pharmacy,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
通讯作者单位	临床药学与药理系
推荐引用方式 GB/T 7714	Dai, Da-Peng,Hu, Li-Ming,Geng, Pei-Wu,et al. In vitro functional analysis of 24 novel CYP2C19 variants recently found in the Chinese Han population[J]. XENOBIOTICA,2015,45(11):1030-1035.
APA	Dai, Da-Peng., Hu, Li-Ming., Geng, Pei-Wu., Wang, Shuang-Hu., Cai, Jie., ... & Cai, Jian-Ping. (2015). In vitro functional analysis of 24 novel CYP2C19 variants recently found in the Chinese Han population. XENOBIOTICA, 45(11), 1030-1035.
MLA	Dai, Da-Peng,et al."In vitro functional analysis of 24 novel CYP2C19 variants recently found in the Chinese Han population".XENOBIOTICA 45.11(2015):1030-1035.