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