Relling M V, Hoffman J M
Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Clin Pharmacol Ther. 2007 Mar;81(3):425-8. doi: 10.1038/sj.clpt.6100097.
The field of pharmacogenetics has existed since the 1950s, when it was demonstrated that some drug effects could differ substantially among race and ethnic groups, and that some drug metabolizing enzyme activities were inherited. During the 1990s, application of molecular biology to the study of inherited drug-related phenotypes proved the genetic basis of several genetic polymorphisms. Genomic technology has now demonstrated that germline genetic variability among humans is extremely common. The combined weight of proven examples whereby pharmacogenetics affects drugs, and the possibility of even more examples being elucidated in the coming decades, dictates that pharmacogenetics be incorporated into the drug approval process. It is our contention that minimal pharmacogenetic testing should be required for all new drug applications to the Food and Drug Administration (FDA). This would include a requirement for germline DNA to be prospectively collected from all subjects participating in preapproval clinical trials. For drugs that are metabolized by enzymes whose genes have clearly inactivating polymorphisms, clinical trial participants should be genotyped for those polymorphisms.
药物遗传学领域自20世纪50年代就已存在，当时有研究表明，某些药物效应在不同种族和族裔群体之间可能存在显著差异，而且一些药物代谢酶的活性是可遗传的。在20世纪90年代，将分子生物学应用于遗传性药物相关表型的研究证实了几种基因多态性的遗传基础。基因组技术现已表明，人类种系基因变异极为常见。药物遗传学影响药物的已证实实例的综合影响力，以及未来几十年可能会阐明更多实例的可能性，决定了药物遗传学应纳入药物审批过程。我们认为，向美国食品药品监督管理局（FDA）提交的所有新药申请都应要求进行最低限度的药物遗传学检测。这将包括一项要求，即前瞻性地收集所有参与批准前临床试验的受试者的种系DNA。对于那些由具有明确失活多态性基因的酶代谢的药物，临床试验参与者应进行这些多态性的基因分型。
