title: Analysis of genetic variations in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 genes using oligonucleotide microarray.
abstract: The cytochrome P450 enzymes play a critical role in the metabolism of many commonly prescribed drugs. Among them, the most important enzymes are highly polymorphic CYP2C9, CYP2C19, CYP2D6 and CYP3A5, which are responsible for about 40% of the metabolism of clinical used drugs. Here we developed a novel CYP450 oligonucleotide microarray that allow for detection of 32 known variations of CYP genes from a single multiplex reaction, including 19 polymorphisms of CYP2D6 gene, 8 polymorphisms of CYP2C9 gene, 4 polymorphisms of CYP2C19 gene and 1 polymorphism of CYP3A5 gene. 229 genomic DNA samples from unrelated Han subjects were analyzed. The microarray results showed to have high call rate and accuracy according to concordance with genotypes identified by independent bidirectional sequencing. Furthermore, we found that the major CYP2C9, CYP2C19, CYP2D6 and CYP3A5 alleles in Chinese Han population were CYP2C9*3 (allelic frequency of 10.7%), CYP2C9*2 (20.31%), CYP2C19*2 (5.68%), CYP2D6*10 (58.52%), CYP2D6*2 (13.76) and CYP3A5*3 (70.69%). With flexible DNA preparation, the microarray can significantly facilitates the process of detecting genetics variations in CYP2C9, CYP2C19, CYP2D6 and CYP3A5 gene and provide safe and effective therapy for individual patients.
authors.affiliation: Ministry of Education Engineering Research Center of Bioreactor and Pharmaceutical Development, Jilin Agricultural University Changchun, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: National Engineering Center for Biochip at Shanghai Shanghai, China.
authors.forename: Huasheng
authors.initials: H
authors.lastname: Xiao
authors.affiliation: National Engineering Center for Biochip at Shanghai Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: National Engineering Center for Biochip at Shanghai Shanghai, China.
authors.forename: Chunxiu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Ministry of Education Engineering Research Center of Bioreactor and Pharmaceutical Development, Jilin Agricultural University Changchun, China.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Liu
authors.affiliation: Ministry of Education Engineering Research Center of Bioreactor and Pharmaceutical Development, Jilin Agricultural University Changchun, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yao
authors.affiliation: National Engineering Center for Biochip at Shanghai Shanghai, China.
authors.forename: Haihui
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Ministry of Education Engineering Research Center of Bioreactor and Pharmaceutical Development, Jilin Agricultural University Changchun, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
keywords: CYP2C19; CYP2C9; CYP2D6; CYP3A5; Polymorphism; microarray