Expression and functional characterization of a new CYP2C9 variant

摘要

CYP2C9,a major isoform of the CYP2C subfamily that comprises about 20% of the total cytochrome P450 protein in liver microsomes,and is involved in the metabolism of 16% clinical drugs such as S-warfarin,tolbutamide,phenytoin and several nonsteroidal anti-inflammatory drug.By now 12 kinds of CYP2C9 allele variants have been found,whose distribution in different race and catalytic activities have been widely studied.Recently we found a new CYP2C9 variant(CYP2C9 13)from a poor metabolizer Chinese of lornoxicam.It is a T269C transversion in exon 2 of CYP2C9 that leads to a leu90Pro substitution in the encoded protein.Frenquency analysis shows that approximately 2% of Chinese population carries the allele.A part of person with the new CYP2C9 allele heterozygote had reduced intrinsic clearance of lornoxicam in vivo.In order to further study its catalytic activity in vitro,we expressed the new CYP2C9 variant from COS-7 cells transfected by the recombinant vector of pCDNA3.1-CYP2C9 with a T269C change of CYP2C9.