Avery Peter, Mousa Shaymaa S, Mousa Shaker A
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Pharmgenomics Pers Med. 2009;2:79-91. doi: 10.2147/pgpm.s5806. Epub 2009 Sep 13.
Advances in genotype technology in the last decade have put the pharmacogenomics revolution at the forefront of future medicine in clinical practice. Discovery of novel gene variations in drug transporters, drug targets, effector proteins and metabolizing enzymes in the form of single-nucleotide polymorphisms (SNPs) continue to provide insight into the biological phenomena that govern drug efficacy and toxicity. To date, novel gene discoveries extracted from genome-wide association scans and candidate gene studies in at least four antidiabetic drug classes have helped illuminate possible causes of interindividual variability in response. Inadequate protocol guidelines for pharmacogenomics studies often leads to poorly designed studies, making it hard to formulate a definitive conclusion regarding the clinical relevance of the information at hand. These issues, along with the ethical, social, political, legislative, technological, and economic challenges associated with pharmacogenomics have only delayed its entry to mainstream clinical practice. On the other hand, these issues are being actively pursued and rapid progress is being made in each area which assures the possibility of gaining widespread acceptance in clinical practice.
在过去十年中,基因分型技术的进展已使药物基因组学革命处于临床实践中未来医学的前沿。以单核苷酸多态性(SNP)形式发现的药物转运体、药物靶点、效应蛋白和代谢酶中的新型基因变异,继续为支配药物疗效和毒性的生物学现象提供见解。迄今为止,从至少四类抗糖尿病药物的全基因组关联扫描和候选基因研究中提取的新型基因发现,有助于阐明个体间反应差异的可能原因。药物基因组学研究的方案指南不完善,常常导致研究设计不佳,难以就手头信息的临床相关性得出明确结论。这些问题,连同与药物基因组学相关的伦理、社会、政治、立法、技术和经济挑战,只是推迟了其进入主流临床实践的时间。另一方面,这些问题正在积极研究中,并且在每个领域都正在取得迅速进展,这确保了在临床实践中获得广泛接受的可能性。