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学科主题: 临床医学
题名:
Characterization of a Novel CYP2C9 Mutation (1009C > A) Detected in a Warfarin-Sensitive Patient
作者: Luo, Shun-Bin1; Li, Chuan-Bao2; Dai, Da-Peng3,4; Wang, Shuang-Hu1,5; Wang, Zhen-He1; Geng, Pei-Wu1; Cai, Jie1; Jiang, Zhe-Li1; Pu, Cheng-Wei6; Shang, Ke6; Yuan, Xin-Min7,8; Cao, Ya-Po9; Hu, Guo-Xin1; Cai, Jian-Ping1
关键词: CYP2C9 ; allelic variant ; insect cell microsome ; functional analysis in vitro
刊名: JOURNAL OF PHARMACOLOGICAL SCIENCES
发表日期: 2014-06-01
DOI: 10.1254/jphs.13189FP
卷: 125, 期:2, 页:150-156
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: IN-VITRO ; FUNCTIONAL-CHARACTERIZATION ; GENETIC POLYMORPHISMS ; DOSE REQUIREMENT ; ALLELIC VARIANTS ; CHINESE PATIENTS ; METABOLISM ; CYTOCHROME-P450 ; POPULATION ; GENOTYPE
英文摘要:

Warfarin is the most frequently prescribed anticoagulant for the long-term treatment in the clinic. Recent studies have shown that polymorphic alleles within the CYP2C9, VKORC1, and CYP4F2 genes are related to the warfarin dosage requirement. In this study, a novel non-synonymous mutation (1009C>A) in CYP2C9 was detected in a warfarin-hypersensitive patient, while the other two candidate genes were both found to be homozygous for the wild-type alleles. The newly identified point mutation results in an amino acid substitution at position 337 of the CYP2C9 protein (P337T) and has been designated as the novel allele CYP2C9*58. When expressed in insect cell microsomes, the relative intrinsic clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite similar to those of the typical defective variant CYP2C9.3, whereas the clearance value of CYP2C9.58 for diclofenac was slightly higher than that of another typical defective variant CYP2C9.2. These data suggested that when compared with wild-type CYP2C9.1, the enzymatic activity of the novel allelic variant has been greatly reduced by the 1009C>A mutation. If patients carrying this allele take drugs metabolized by CYP2C9, their metabolic rate might be slower than that of wild-type allele carriers and thus much more attention should be paid to their clinical care.

语种: 英语
所属项目编号: 201302008 ; 31371280
项目资助者: Ministry of Health of the People&prime ; s Republic of China ; National Natural Science Foundation of China
WOS记录号: WOS:000338272500005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67832
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: 1.Minist Hlth, Beijing Hosp, Clin Lab, Beijing 100730, Peoples R China
2.Beijing Hosp, Key Lab Geriatr, Beijing 100730, Peoples R China
3.Minist Hlth, Beijing Inst Geriatr, Beijing 100730, Peoples R China
4.Wenzhou Med Univ, Dept Pharmacol, Wenzhou 325035, Zhejiang, Peoples R China
5.Peoples Hosp Lishui, Lab Clin Pharm, Lishui 323000, Zhejiang, Peoples R China
6.Peking Univ, Hosp 1, Dept Lab Med, Beijing 100034, Peoples R China
7.Chinese Acad Med Sci, FuWai Hosp, Dept Lab Med, Beijing 100037, Peoples R China
8.Peking Union Med Coll, Beijing 100037, Peoples R China
9.Tsinghua Univ, Hosp 1, Dept Lab Med, Beijing 100016, Peoples R China

Recommended Citation:
Luo, Shun-Bin,Li, Chuan-Bao,Dai, Da-Peng,et al. Characterization of a Novel CYP2C9 Mutation (1009C > A) Detected in a Warfarin-Sensitive Patient[J]. JOURNAL OF PHARMACOLOGICAL SCIENCES,2014,125(2):150-156.
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