Department of Immunology, Faculty of Health Sciences, University of Pretoria, South Africa.
Pharmacol Ther. 2012 Mar;133(3):280-90. doi: 10.1016/j.pharmthera.2011.11.002. Epub 2011 Nov 22.
Human genetic variation in the form of single nucleotide polymorphisms as well as more complex structural variations such as insertions, deletions and copy number variants, is partially responsible for the clinical variation seen in response to pharmacotherapeutic drugs. This affects the likelihood of experiencing adverse drug reactions and also of achieving therapeutic success. In this paper, we review key studies in cardiovascular pharmacogenetics that reveal genetic variations underlying the outcomes of drug treatment in cardiovascular disease. Examples of genetic associations with drug efficacy and toxicity are described, including the roles of genetic variability in pharmacokinetics (e.g. drug metabolizing enzymes) and pharmacodynamics (e.g. drug targets). These findings have functional implications that could lead to the development of genetic tests aimed at minimizing drug toxicity and optimizing drug efficacy in cardiovascular medicine.
人类遗传变异形式,如单核苷酸多态性,以及更复杂的结构变异,如插入、缺失和拷贝数变异,部分导致了药物治疗反应中的临床变异。这影响了患者发生药物不良反应的可能性,也影响了获得治疗成功的可能性。本文综述了心血管药物遗传学中的关键研究,这些研究揭示了药物治疗心血管疾病结局的遗传基础。描述了与药物疗效和毒性相关的遗传关联的例子,包括药物代谢动力学(如药物代谢酶)和药效学(如药物靶点)中遗传变异性的作用。这些发现具有功能意义,可能导致开发旨在减少心血管药物毒性和优化药物疗效的遗传检测。