Weinshilboum Richard M, Wang Liewei
Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Mayo Medical School-Mayo Foundation, Rochester, Minnesota 55905, USA.
Annu Rev Genomics Hum Genet. 2006;7:223-45. doi: 10.1146/annurev.genom.6.080604.162315.
Pharmacogenetics and pharmacogenomics involve the study of the role of inheritance in individual variation in drug response, a phenotype that varies from potentially life-threatening adverse drug reactions to equally serious lack of therapeutic efficacy. This discipline evolved from the convergence of rapid advances in molecular pharmacology and genomics. Originally, pharmacogenetic studies focused on monogenic traits, often involving genetic variation in drug metabolism. However, contemporary studies increasingly involve entire "pathways" encoding proteins that influence both pharmacokinetics--factors that influence the concentration of a drug reaching its target(s)--and pharmacodynamics, the drug target itself, as well as genome-wide approaches. Pharmacogenomics is also increasingly moving across the "translational interface" into the clinic and is being incorporated into the drug development process and the governmental regulation of that process. However, significant challenges remain to be overcome if pharmacogenetics-pharmacogenomics is to achieve its full potential as a major medical application of genomic science.
药物遗传学和药物基因组学研究遗传因素在个体药物反应差异中所起的作用，这种表型差异涵盖了从可能危及生命的药物不良反应到同样严重的治疗效果不佳等各种情况。这一学科是分子药理学和基因组学快速发展融合的产物。最初，药物遗传学研究聚焦于单基因性状，通常涉及药物代谢中的基因变异。然而，当代研究越来越多地涉及编码影响药物代谢动力学（影响药物到达靶点浓度的因素）和药效学（药物靶点本身）的蛋白质的整个“通路”，以及全基因组方法。药物基因组学也越来越多地跨越“转化界面”进入临床，并被纳入药物研发过程及该过程的政府监管之中。然而，如果药物遗传学 - 药物基因组学要充分发挥其作为基因组科学主要医学应用的全部潜力，仍有重大挑战有待克服。
