Kim Jason Yongha, Cheong Hyun Sub, Park Tae-Joon, Shin Hee Jung, Seo Doo Won, Na Han Sung, Chung Myeon Woo, Shin Hyoung Doo
Department of Life Science, Sogang University, SNP Genetics, Inc., Seoul 121-742, Republic of Korea.
Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul 121-742, Republic of Korea.
Biomed Rep. 2014 Jul;2(4):463-476. doi: 10.3892/br.2014.272. Epub 2014 Apr 30.
Pharmacogenomics is the study of the association between inter-individual genetic differences and drug responses. Researches in pharmacogenomics have been performed in compliance with the use of several genotyping technologies. In this study, a total of 392 single-nucleotide polymorphisms (SNPs) located in 141 pharmacogenes, including 21 phase I, 13 phase II, 18 transporter and 5 modifier genes, were selected and genotyped in 150 subjects using the GoldenGate assay or the SNaPshot technique. These variants were in Hardy-Weinberg equilibrium (HWE) (P>0.05), except for 22 SNPs. Genotyping of the 392 SNPs revealed that the minor allele frequencies of 47 SNPs were <0.05, 105 SNPs were monomorphic and 22 variants were not in HWE. Also, based on previous studies, we predicted the association between the polymorphisms of certain pharmacogenes, such as cytochrome P450 2D6, cytochrome P450 2C9, vitamin K epoxide reductase complex, subunit 1, cytochrome P450 2C19, human leukocyte antigen, class I, B and thiopurine S-methyltransferase, and drug efficacy. In conclusion, our study demonstrated the allele distribution of SNPs in 141 pharmacogenes as determined by high-throughput screening. Our results may be helpful in developing personalized medicines by using pharmacogene polymorphisms.
药物基因组学是研究个体间基因差异与药物反应之间的关联。药物基因组学的研究是按照几种基因分型技术的使用来进行的。在本研究中,共选择了位于141个药物代谢基因中的392个单核苷酸多态性(SNP),包括21个I相、13个II相、18个转运体和5个修饰基因,并使用GoldenGate检测法或SNaPshot技术对150名受试者进行基因分型。除22个SNP外,这些变异处于哈迪-温伯格平衡(HWE)(P>0.05)。对392个SNP的基因分型显示,47个SNP的次要等位基因频率<0.05,105个SNP是单态的,22个变异不处于HWE。此外,基于先前的研究,我们预测了某些药物代谢基因的多态性之间的关联,如细胞色素P450 2D6、细胞色素P450 2C9、维生素K环氧化物还原酶复合体亚基1、细胞色素P450 2C19、人类白细胞抗原I类B和硫嘌呤S-甲基转移酶与药物疗效之间的关联。总之,我们的研究通过高通量筛选确定了141个药物代谢基因中SNP的等位基因分布。我们的结果可能有助于利用药物代谢基因多态性开发个性化药物。