functional characterisation of human cyp2c9 allelic variants in cos-7 cells

Clicks: 189
ID: 210859
2016
Article Quality & Performance Metrics
Overall Quality Improving Quality
0.0 /100
Combines engagement data with AI-assessed academic quality
AI Quality Assessment
Not analyzed
Abstract
Variability in activity of CYP2C9, which is involved in the metabolism of approximately 15% of current therapeutic drugs, is an important contributor to interindividual differences in drug response. To evaluate the functional alternations of CYP2C9*2, CYP2C9*3, CYP2C9*8, CYP2C9*11 and CYP2C9*31, identified in our previous study in Chinese Han population, allelic variants as well as the wild-type CYP2C9 were transiently expressed in COS-7 cells. Kinetic parameters (Km, Vmax and Clint) for S-warfarin 7-hydroxylation by these recombinant CYP2C9s were determined. Relative to CYP2C9.1, recombinant CYP2C9.3 and CYP2C9.11 exhibited significantly higher Km values, and all allelic variants showed significantly decreased Vmax and Clint values. Among all allelic variants, catalytic activity of CYP2C9.3 and CYP2C9.11 reduced the most (8.2% and 9.8% of Clint ratio, respectively; P<0.001). These findings should be useful for predicting the phenotype profiles of CYP2C9 in Chinese Han population, comparing the functional results of these alleles accurately, and finally optimizing pharmacotherapy of drug treatment.
Reference Key
edu2016frontiersfunctional Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Huihui eDu;Zhiyun eWei;Yucai eYan;Yuyu eXiong;Xiaoqing eZhang;Lu eShen;Yunfeng eRuan;Xi eWu;Qingqing eXu;Lin eHe;Shengying eQin
Journal chemical research in chinese universities
Year 2016
DOI 10.3389/fphar.2016.00098
URL
http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00098/full
Keywords
HPLC pharmacokinetics in vitro models cytochrome p450 genetic polymorphisms pharmacology chinese hantherapeutics

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.