Daly Ann K
Institute of Cellular Medicine, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Genome Med. 2013 Jan 29;5(1):5. doi: 10.1186/gm409. eCollection 2013.
Considerable progress has been made in identifying genetic risk factors for idiosyncratic adverse drug reactions in the past 30 years. These reactions can affect various tissues and organs, including liver, skin, muscle and heart, in a drug-dependent manner. Using both candidate gene and genome-wide association studies, various genes that make contributions of varying extents to each of these forms of reactions have been identified. Many of the associations identified for reactions affecting the liver and skin involve human leukocyte antigen (HLA) genes and for reactions relating to the drugs abacavir and carbamazepine, HLA genotyping is now in routine use prior to drug prescription. Other HLA associations are not sufficiently specific for translation but are still of interest in relation to underlying mechanisms for the reactions. Progress on non-HLA genes affecting adverse drug reactions has been less, but some important associations, such as those of SLCO1B1 and statin myopathy, KCNE1 and drug-induced QT prolongation and NAT2 and isoniazid-induced liver injury, are considered. Future prospects for identification of additional genetic risk factors for the various adverse drug reactions are discussed.
在过去30年里，在确定特异质性药物不良反应的遗传风险因素方面取得了相当大的进展。这些反应可依药物的不同而影响包括肝脏、皮肤、肌肉和心脏在内的各种组织和器官。通过使用候选基因研究和全基因组关联研究，已经确定了对每种这些反应形式有不同程度贡献的各种基因。已确定的与影响肝脏和皮肤反应相关的许多关联涉及人类白细胞抗原（HLA）基因，对于与阿巴卡韦和卡马西平药物相关的反应，现在在药物处方前常规使用HLA基因分型。其他HLA关联对于转化应用而言特异性不足，但对于反应的潜在机制仍具有研究意义。在影响药物不良反应的非HLA基因方面进展较少，但文中考虑了一些重要的关联，如SLCO1B1与他汀类药物所致肌病、KCNE1与药物诱导的QT间期延长以及NAT2与异烟肼所致肝损伤之间的关联。文中还讨论了识别各种药物不良反应的其他遗传风险因素的未来前景。
