Terra Steven G, Johnson Julie A
Department of Pharmacy Practice, University of Florida, Gainesville, Florida 32610, USA.
Am J Cardiovasc Drugs. 2002;2(5):287-96. doi: 10.2165/00129784-200202050-00001.
The completion of sequencing of the human genome will be the vanguard for numerous advances in medicine. The first discernible application is likely to occur in pharmacogenomics, a field focused on the influence of genetic differences on the variability in patients' response to medications. While an inherited basis for drug response has been recognized for some time, it is the confluence of molecular biology, high-throughput genotyping, and bioinformatics that has made it practical to study the genetic basis of variability to medications on a large scale. Pharmacogenomics may enable clinicians to prospectively identify patients most likely to derive benefit from a drug, with minimal likelihood of adverse events. This DNA-based approach to predicting clinical drug efficacy and toxicity would shift the current prescribing paradigm from its empirical nature to a more patient-specific model, ushering in a new era of personalized medicine. Polymorphisms in drug metabolizing enzymes, drug targets, and disease pathogenesis genes are associated with therapeutic effect to cardiovascular pharmacotherapy. Moreover, pharmacogenomics and functional genomics are expected to have a profound impact on the process of drug discovery and development. Finally, pharmacogenomics is likely to transform the way clinical trials are conducted by allowing for the selection of a more homogeneous study population, thereby reducing the size and cost of clinical investigation.
人类基因组测序的完成将成为医学众多进展的先锋。首个可识别的应用可能出现在药物基因组学领域，该领域专注于基因差异对患者药物反应变异性的影响。虽然药物反应的遗传基础在一段时间前就已被认识到，但正是分子生物学、高通量基因分型和生物信息学的融合，使得大规模研究药物反应变异性的遗传基础变得切实可行。药物基因组学可使临床医生前瞻性地识别出最有可能从某种药物中获益且发生不良事件可能性最小的患者。这种基于DNA预测临床药物疗效和毒性的方法将把当前基于经验的处方模式转变为更具患者特异性的模式，开创个性化医疗的新时代。药物代谢酶、药物靶点和疾病发病机制基因中的多态性与心血管药物治疗的疗效相关。此外，药物基因组学和功能基因组学有望对药物研发过程产生深远影响。最后，药物基因组学可能会改变临床试验的开展方式，通过选择更同质化的研究人群，从而降低临床研究的规模和成本。
