Zhang Wei, Huang R Stephanie, Dolan M Eileen
Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Trends Cancer Res. 2008;4:1-13.
The field of pharmacogenomics is challenging because of the multigenic nature of drug response and toxicity. The candidate gene approach has been traditionally utilized to determine the contribution of genetic variation to a particular phenotype; however, the sequencing of the human genome and the genetic resource provided by the International HapMap Project has allowed researchers to perform genome-wide studies without a priori knowledge. Recent work has demonstrated the usefulness of cell-based models for pharmacogenomic discovery using the HapMap samples, which are a panel of well-genotyped, human lymphoblastoid cell lines (LCLs) derived from 90 Utah residents with ancestry from northern and western Europe (CEU), 90 Yoruba in Ibadan, Nigeria (YRI), 45 Japanese in Tokyo, Japan (JPT) and 45 Han Chinese in Beijing, China (CHB). Using these cell-based models, investigators are able to study not only individual variation in drug response, but also population differences in drug response. Finally, besides single nucleotide polymorphisms (SNPs) and gene expression, these cell-based models can also be used to investigate other genetic (e.g. copy number variants, CNVs), epigenetic or environmental factors responsible for drug response.
由于药物反应和毒性的多基因性质，药物基因组学领域具有挑战性。传统上，候选基因方法被用于确定基因变异对特定表型的影响；然而，人类基因组测序以及国际人类基因组单体型图计划（International HapMap Project）提供的遗传资源，使研究人员能够在没有先验知识的情况下进行全基因组研究。最近的研究表明，利用人类基因组单体型图样本建立的基于细胞的模型在药物基因组学发现中很有用，这些样本是一组经过良好基因分型的人类淋巴母细胞系（LCLs），来源于90名有北欧和西欧血统的犹他州居民（CEU）、90名尼日利亚伊巴丹的约鲁巴人（YRI）、45名日本东京的日本人（JPT）以及45名中国北京的汉族人（CHB）。利用这些基于细胞的模型，研究人员不仅能够研究药物反应中的个体差异，还能够研究药物反应中的群体差异。最后，除了单核苷酸多态性（SNP）和基因表达外，这些基于细胞的模型还可用于研究其他与药物反应有关的遗传因素（如拷贝数变异，CNV）、表观遗传因素或环境因素。
