Division of Cardiovascular Diseases, Scripps Clinic, Scripps Translational Science Institute, La Jolla, CA, USA.
Wiley Interdiscip Rev Syst Biol Med. 2011 Mar-Apr;3(2):206-15. doi: 10.1002/wsbm.113. Epub 2010 Aug 20.
Over one-fourth of the 36 million annual outpatient prescriptions filled in the United States are known to have human genomic biomarker information available that predicts drug safety and efficacy, or both. However, to date, we have not systematically implemented strategies to effectively use this data in clinical practice to improve patient outcomes. Part of the difficulty has stemmed from the only modest predictive capacity of previously identified gene variants, lack of replication of data in multiple studies, and the hesitancy of the clinical community to translate data gleaned from basic and translational research to routine clinical practice. Now, additional key variants that strongly impact drug absorption, metabolism, and excretion are rapidly surfacing through the use of genome-wide association technology. Most importantly, these variants are being validated in independent cohorts of thousands of cases and controls. In the near future, the dramatic reduction in the cost of DNA sequencing will lead to further insight into the common and rare genetic variants that strongly predict our individual response to commonly used medications. The clinical community will need to be prepared to utilize this vital data in aiding their selection of the right drug for the right patient if we expect to significantly reduce the ever increasing burden of societies' most common diseases. Herein, we detail the most clinically compelling and robust examples of pharmacogenomics emerging in the field of cardiovascular disease and hopefully foretell how cardiovascular disease might be treated in the era of genomic medicine.
已知美国每年开出的 3600 万张门诊处方中,有超过四分之一的处方都含有可预测药物安全性和疗效(或两者兼具)的人类基因组生物标志物信息。然而,迄今为止,我们尚未系统地制定策略,以便在临床实践中有效利用这些数据来改善患者的预后。部分困难源自先前确定的基因变异预测能力有限、多个研究的数据缺乏复制,以及临床界不愿意将从基础和转化研究中获得的数据转化为常规临床实践。现在,通过使用全基因组关联技术,更多可强烈影响药物吸收、代谢和排泄的关键变异正在迅速显现。最重要的是,这些变异正在数千例独立病例和对照的队列中得到验证。在不久的将来,DNA 测序成本的大幅降低将进一步深入了解常见和罕见的遗传变异,这些变异强烈预测我们对常用药物的个体反应。如果我们期望显著降低社会上最常见疾病的负担不断增加,临床界就需要准备好利用这些重要数据来帮助他们为合适的患者选择合适的药物。在此,我们详细介绍了心血管疾病领域中涌现的最具临床说服力和最稳健的药物基因组学实例,并希望预测在基因组医学时代心血管疾病将如何得到治疗。