Mosher Carrie M, Court Michael H
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Handb Exp Pharmacol. 2010(199):49-77. doi: 10.1007/978-3-642-10324-7_3.
Pharmacogenomics is the study of the impact of genetic variation on drug effects, with the ultimate goal of achieving "personalised medicine". Since the completion of the Human Genome Project, great strides have been made towards the goal of personalised dosing of drugs in people, as exemplified by the development of gene-guided dosing of the anticoagulant drug, warfarin. Although the pharmacogenomics of domestic animals is still at an early stage of development, there is great potential for advances in the coming years as the direct result of complete genome sequences currently being derived for many of the species of significance to veterinary and comparative medicine. This sequence information is being used to discover sequence variants in candidate genes associated with altered drug response, as well as to develop whole genome high density single nucleotide polymorphism arrays for genotype-phenotype linkage analysis. This review summarises the current state of veterinary pharmacogenomics research, including drug response variability phenotypes with either known genetic aetiology or strong circumstantial evidence for genetic involvement. Polymorphisms and rarer gene variants affecting drug disposition (pharmacokinetics) and drug effect (pharmacodynamics) are discussed. In addition to providing the veterinary clinician with useful information for the practise of therapeutics, it is envisaged that the increasing knowledge base will also provide a resource for individuals involved in veterinary and comparative biomedical research.
药物基因组学是研究基因变异对药物效应的影响，其最终目标是实现“个性化医疗”。自人类基因组计划完成以来，在实现针对人类的药物个性化给药目标方面已取得了巨大进展，抗凝药物华法林的基因导向给药的发展就是例证。尽管家畜的药物基因组学仍处于发展初期，但由于目前正在为许多对兽医和比较医学具有重要意义的物种推导完整的基因组序列，未来几年有望取得巨大进展。这些序列信息正被用于发现与药物反应改变相关的候选基因中的序列变异，以及开发用于基因型-表型连锁分析的全基因组高密度单核苷酸多态性阵列。本综述总结了兽医药理学基因组学研究的现状，包括具有已知遗传病因或有强有力的间接证据表明与遗传因素有关的药物反应变异性表型。讨论了影响药物处置（药代动力学）和药物效应（药效动力学）的多态性和罕见基因变异。除了为兽医临床医生提供治疗实践的有用信息外，预计不断增加的知识库也将为从事兽医和比较生物医学研究的人员提供资源。
