Linder M W, Valdes R
Department of Pathology and Laboratory Medicine, School of Medicine, University of Louisville, KY 40292, USA.
Ann Clin Lab Sci. 1999 Apr-Jun;29(2):140-9.
Metabolism and disposition of foreign compounds, including pharmaceuticals, is dependent upon a host of factors. However, a genetic basis for individuality in drug metabolism has long been recognized and more recently has been confirmed. It is now well understood that a finite number of inherited sequence variants (alleles) of genes encoding drug-metabolizing enzymes give rise to discrete drug metabolism phenotypes. This primer in pharmacogenetics will introduce the clinical laboratorian to the mechanistic basis underlying the influence of genetics on pharmacology. We begin with an overview of pharmacology and introduce the importance of protein structure in maintaining steady-state drug concentrations. After review of fundamental concepts related to drug-metabolizing enzymes and genetics, we then give examples of how discrete genetic variations (polymorphism) alter the response (phenotype) to certain therapeutics in select individuals. We conclude with several analytical and interpretive considerations which must be considered by laboratories offering pharmacogenetic services.
包括药物在内的外来化合物的代谢和处置取决于许多因素。然而，药物代谢个体差异的遗传基础早已被认识到，并且最近得到了证实。现在人们已经清楚地认识到，编码药物代谢酶的基因中有限数量的遗传序列变异（等位基因）会导致离散的药物代谢表型。这本药物遗传学入门读物将向临床检验人员介绍遗传学对药理学影响的机制基础。我们首先概述药理学，并介绍蛋白质结构在维持稳态药物浓度方面的重要性。在回顾了与药物代谢酶和遗传学相关的基本概念之后，我们接着举例说明离散的基因变异（多态性）如何改变特定个体对某些治疗药物的反应（表型）。我们最后提出了提供药物遗传学服务的实验室必须考虑的几个分析和解释方面的注意事项。
