Effects of 22 Novel CYP2D6 Variants Found in the Chinese Population on the Bufuralol and Dextromethorphan Metabolisms In Vitro

doi:10.1111/bcpt.12478

科研成果详情

题名	Effects of 22 Novel CYP2D6 Variants Found in the Chinese Population on the Bufuralol and Dextromethorphan Metabolisms In Vitro
作者	Cai, Jie 1,2,3; Dai, Da-Peng 1; Geng, Pei-Wu 4; Wang, Shuang-Hu 4; Wang, Hao 2; Zhan, Yun-Yun 2; Huang, Xiang-Xin 2; Hu, Guo-Xin2; Cai, Jian-Ping 1
发表日期	2016-03
发表期刊	BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	HUMAN CYTOCHROME-P450 2D6 ; ALLELIC VARIANTS ; FUNCTIONAL-CHARACTERIZATION ; GENETIC POLYMORPHISMS ; JAPANESE POPULATION ; DRUG DEVELOPMENT ; HAN POPULATION ; ENZYMES ; ASIANS ; PHARMACOGENOMICS
摘要	Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic enzyme that metabolizes a large number of therapeutic drugs. To date, more than 100 CYP2D6 allelic variants have been reported. Among these variants, we recently identified 22 novel variants in the Chinese population. The aim of this study was to functionally characterize the enzymatic activity of these variants in vitro. A baculovirus-mediated expression system was used to express wild-type CYP2D6.1 and other variants (CYP2D6.2, CYP2D6.10 and 22 novel CYP2D6 variants) at high levels. Then, the insect microsomes containing expressed CYP2D6 proteins were incubated with bufuralol or dextromethorphan at 37 degrees C for 20 or 25 min., respectively. After termination, the metabolites were extracted and used for the detection with high-performance liquid chromatography. Among the 24 CYP2D6 variants tested, two variants (CYP2D6.92 and CYP2D6.96) were found to be catalytically inactive. The remaining 22 variants exhibited significantly decreased intrinsic clearance values for bufuralol 1-hydroxylation and 20 variants showed significantly lower intrinsic clearance values for dextromethorphan O-demethylation than those of the wild-type CYP2D6.1. Our in vitro results suggest that most of the variants exhibit significantly reduced catalytic activities compared with the wild-type, and these data provide valuable information for personalized medicine in Chinese and other Asian populations.
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	WILEY-BLACKWELL
出版地	HOBOKEN
ISSN	1742-7835
EISSN	1742-7843
卷号	118 期号:3 页码:190-199
DOI	10.1111/bcpt.12478
页数	10
WOS类目	Pharmacology & Pharmacy ; Toxicology
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
WOS记录号	WOS:000370318400004
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	26310775
SCOPUSEID	2-s2.0-84983111449
通讯作者地址	[Cai, Jian-Ping]The Key Laboratory of Geriatrics,Beijing Hospital and Beijing Institute of Geriatrics,Ministry of Health,Beijing,100730,China
Scopus学科分类	Toxicology;Pharmacology
引用统计	被引频次：18[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/9362
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	Cai, Jian-Ping
作者单位	1.The Key Laboratory of Geriatrics,Beijing Hospital and Beijing Institute of Geriatrics,Ministry of Health,Beijing,China; 2.Department of Pharmacology,School of Pharmacy of Wenzhou Medical University,Wenzhou,325035,China; 3.Department of Pharmacy,Traditional Chinese Medical Hospital of Wenling,Wenling,China; 4.The Laboratory of Clinical Pharmacy,The People's Hospital of Lishui,Lishui,China
第一作者单位	临床药学与药理系
推荐引用方式 GB/T 7714	Cai, Jie,Dai, Da-Peng,Geng, Pei-Wu,et al. Effects of 22 Novel CYP2D6 Variants Found in the Chinese Population on the Bufuralol and Dextromethorphan Metabolisms In Vitro[J]. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY,2016,118(3):190-199.
APA	Cai, Jie., Dai, Da-Peng., Geng, Pei-Wu., Wang, Shuang-Hu., Wang, Hao., ... & Cai, Jian-Ping. (2016). Effects of 22 Novel CYP2D6 Variants Found in the Chinese Population on the Bufuralol and Dextromethorphan Metabolisms In Vitro. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 118(3), 190-199.
MLA	Cai, Jie,et al."Effects of 22 Novel CYP2D6 Variants Found in the Chinese Population on the Bufuralol and Dextromethorphan Metabolisms In Vitro".BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY 118.3(2016):190-199.