Effect of 36 CYP2C9 variants found in the Chinese population on losartan metabolism in vitro

doi:10.3109/00498254.2013.820007

科研成果详情

题名	Effect of 36 CYP2C9 variants found in the Chinese population on losartan metabolism in vitro
作者	Wang, Yu-Han1; Pan, Pei-Pei 2; Dai, Da-Peng 3; Wang, Shuang-Hu 2; Geng, Pei-Wu 2; Cai, Jian-Ping 3; Hu, Guo-Xin 2
发表日期	2014-03
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	Allelic variant catalytic activity CYP2C9 losartan
其他关键词	GENETIC POLYMORPHISMS ; ALLELIC VARIANTS ; INDIAN POPULATION ; PHARMACOKINETICS ; CYTOCHROME-P450 ; IMPACT ; FREQUENCIES
摘要	1. CYP2C9 is an important member of the cytochrome P450 enzyme superfamily, with 57 CYP2C9 allelic variants being previously reported. Among these variants, we recently identified 21 novel alleles (36-56) in the Han Chinese population. The aim of this study was to assess the catalytic activities of 36 CYP2C9 variants found in the Chinese population toward losartan in vitro. 2. Insect microsomes expressing the 36 CYP2C9 variants were incubated with 0.5-25 mu M losartan for 30 min at 37 degrees C. Next, the products were extracted, and signal detection was performed using high-performance liquid chromatography. 3. Compared with wild-type CYP2C9.1, the intrinsic clearance (V-max/K-m) values of all variants except for CYP2C9.56 were significantly altered. One variant exhibited markedly increased values (>250%), whereas 33 variants exhibited significantly decreased values (from 20 to 96%) due to increased K-m and/or decreased V-max values. 4. These findings suggest that more attention should be paid to subjects carrying these infrequent CYP2C9 alleles when administering losartan in the clinic.
资助项目	Ministry of Health of the People's Republic of China [201302008]
出版者	INFORMA HEALTHCARE
出版地	LONDON
ISSN	0049-8254
EISSN	1366-5928
卷号	44 期号:3 页码:270-275
DOI	10.3109/00498254.2013.820007
页数	6
WOS类目	Pharmacology & Pharmacy ; Toxicology
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
WOS记录号	WOS:000332737700009
收录类别	SCIE ; SCOPUS
URL	查看原文
PubMed ID	23844998
SCOPUSEID	2-s2.0-84893696264
通讯作者地址	[Cai, Jian-Ping]Key Laboratory of Geriatrics,Beijing Hospital and Beijing Institute of Geriatrics,Ministry of Health,China
Scopus学科分类	Biochemistry;Toxicology;Pharmacology;Health, Toxicology and Mutagenesis
引用统计	被引频次：29[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/8302
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.Department of Pharmacology,Wenzhou Medical College,Shandong University,China; 2.Key Laboratory of Geriatrics,Beijing Institute of Geriatrics,Ministry of Health,China; 3.Key Laboratory of Geriatrics,Beijing Hospital and Beijing Institute of Geriatrics,Ministry of Health,China
第一作者单位	临床药学与药理系
第一作者的第一单位	临床药学与药理系
推荐引用方式 GB/T 7714	Wang, Yu-Han,Pan, Pei-Pei,Dai, Da-Peng,et al. Effect of 36 CYP2C9 variants found in the Chinese population on losartan metabolism in vitro[J]. XENOBIOTICA,2014,44(3):270-275.
APA	Wang, Yu-Han., Pan, Pei-Pei., Dai, Da-Peng., Wang, Shuang-Hu., Geng, Pei-Wu., ... & Hu, Guo-Xin. (2014). Effect of 36 CYP2C9 variants found in the Chinese population on losartan metabolism in vitro. XENOBIOTICA, 44(3), 270-275.
MLA	Wang, Yu-Han,et al."Effect of 36 CYP2C9 variants found in the Chinese population on losartan metabolism in vitro".XENOBIOTICA 44.3(2014):270-275.