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Characterization of a Novel CYP2C9 Mutation (1009C > A) Detected in a Warfarin-Sensitive Patient
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
2014-06-01
DOI10.1254/jphs.13189FP
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
WOS记录号WOS:000338272500005
项目编号201302008 ; 31371280
资助机构Ministry of Health of the People&prime ; s Republic of China ; National Natural Science Foundation of China
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67832
专题北京大学第一临床医学院
北京大学第一临床医学院_检验科
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
推荐引用方式
GB/T 7714
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.
APA Luo, Shun-Bin.,Li, Chuan-Bao.,Dai, Da-Peng.,Wang, Shuang-Hu.,Wang, Zhen-He.,...&Cai, Jian-Ping.(2014).Characterization of a Novel CYP2C9 Mutation (1009C > A) Detected in a Warfarin-Sensitive Patient.JOURNAL OF PHARMACOLOGICAL SCIENCES,125(2),150-156.
MLA Luo, Shun-Bin,et al."Characterization of a Novel CYP2C9 Mutation (1009C > A) Detected in a Warfarin-Sensitive Patient".JOURNAL OF PHARMACOLOGICAL SCIENCES 125.2(2014):150-156.
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