Wilke Russell A, Lin Debbie W, Roden Dan M, Watkins Paul B, Flockhart David, Zineh Issam, Giacomini Kathleen M, Krauss Ronald M
Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
Nat Rev Drug Discov. 2007 Nov;6(11):904-16. doi: 10.1038/nrd2423.
Serious adverse drug reactions (SADRs) are a major cause of morbidity and mortality worldwide. Some SADRs may be predictable, based upon a drug's pharmacodynamic and pharmacokinetic properties. Many, however, appear to be idiosyncratic. Genetic factors may underlie susceptibility to SADRs and the identification of predisposing genotypes may improve patient management through the prospective selection of appropriate candidates. Here we discuss three specific SADRs with an emphasis on genetic risk factors. These SADRs, selected based on wide-sweeping clinical interest, are drug-induced liver injury, statin-induced myotoxicity and drug-induced long QT and torsades de pointes. Key challenges for the discovery of predictive risk alleles for these SADRs are also considered.
严重药物不良反应（SADR）是全球发病和死亡的主要原因。基于药物的药效学和药代动力学特性，一些SADR可能是可预测的。然而，许多似乎是特异质性的。遗传因素可能是SADR易感性的基础，通过前瞻性地选择合适的患者，识别易感基因型可能改善患者管理。在此，我们重点讨论遗传风险因素，探讨三种特定的SADR。这些SADR是基于广泛的临床关注而选择的，包括药物性肝损伤、他汀类药物引起的肌毒性以及药物引起的长QT间期和尖端扭转型室速。我们还考虑了发现这些SADR预测风险等位基因的关键挑战。
