Identification and characterization of a novel CYP2C9 allelic variant in a warfarin-sensitive patient

doi:10.2217/pgs.15.89

科研成果详情

题名	Identification and characterization of a novel CYP2C9 allelic variant in a warfarin-sensitive patient
作者	Dai, Da-Peng 1; Li, Chuan-Bao 2; Wang, Shuang-Hu 3; Cai, Jie 4; Geng, Pei-Wu 3; Zhou, Yun-Fang 3; Hu, Guo-Xin4; Cai, Jian-Ping 1
发表日期	2015
发表期刊	Pharmacogenomics 影响因子和分区
语种	英语
原始文献类型	Article
关键词	CYP2C9 allelic variants drug metabolism in vitro functional assessment. in vitro functional assessment
其他关键词	GENOME-WIDE ASSOCIATION ; IN-VITRO ASSESSMENT ; DOSE REQUIREMENTS ; FUNCTIONAL-CHARACTERIZATION ; GENOTYPE ; PHARMACOGENETICS ; METABOLISM ; MUTATION
摘要	Aim:To determine the genetic basis of the low warfarin dose requirement in a Chinese patient. Materials & methods:Bi-directional sequencing of CYP2C9, VKORC1 and CYP4F2 genes was performed. CYP2C9 variants were highly expressed in yeast and insect-cell microsomes. Three typical CYP2C9 probe drugs were used to evaluate the catalytic activity. Results:A novel missense mutation (1400 T>C) was identified in CYP2C9 and had been named as new allele *60. When expressed in yeast and insect cells, compared with wild-type enzyme, variant CYP2C9.60 exhibited lower protein expression capacity and showed significantly decreased metabolic activities for the hydroxylation of S-warfarin, tolbutamide and diclofenac. Conclusion:The novel mutation can greatly decrease the enzymatic activity of the CYP2C9 enzyme both in vitro and in vivo.
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	FUTURE MEDICINE LTD
出版地	LONDON
ISSN	1462-2416
EISSN	1744-8042
卷号	16 期号:13 页码:1475-86.
DOI	10.2217/pgs.15.89
页数	12
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000361143100004
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	26255664
SCOPUSEID	2-s2.0-84941616279
通讯作者地址	[Cai, Jian-Ping]Key Laboratory of Geriatrics,Beijing Hospital,Beijing Institute of Geriatrics,Ministry of Health,Beijing,100730,China
Scopus学科分类	Molecular Medicine;Genetics;Pharmacology
引用统计	被引频次：8[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/34281
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.Key Laboratory of Geriatrics,Beijing Hospital,Beijing Institute of Geriatrics,Ministry of Health,Beijing,100730,China; 2.Clinical Laboratory of Beijing Hospital,Ministry of Health,Beijing,100730,China; 3.Laboratory of Clinical Pharmacy,People's Hospital of Lishui,Lishui, Zhejiang,323000,China; 4.Department of Pharmacology,School of Pharmacy,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
推荐引用方式 GB/T 7714	Dai, Da-Peng,Li, Chuan-Bao,Wang, Shuang-Hu,et al. Identification and characterization of a novel CYP2C9 allelic variant in a warfarin-sensitive patient[J]. Pharmacogenomics,2015,16(13):1475-86..
APA	Dai, Da-Peng., Li, Chuan-Bao., Wang, Shuang-Hu., Cai, Jie., Geng, Pei-Wu., ... & Cai, Jian-Ping. (2015). Identification and characterization of a novel CYP2C9 allelic variant in a warfarin-sensitive patient. Pharmacogenomics, 16(13), 1475-86..
MLA	Dai, Da-Peng,et al."Identification and characterization of a novel CYP2C9 allelic variant in a warfarin-sensitive patient".Pharmacogenomics 16.13(2015):1475-86..