de Graaff L C G, van Schaik R H N, van Gelder T
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Neth J Med. 2013 Apr;71(3):145-52.
Taking into account the high frequency of adverse drug reactions (ADRs) in the clinic and taking into account the growing knowledge of the genetic mechanisms underlying some of these ADRs, we believe that every clinician should know at least the basic principles of pharmacogenetics. However, our experience is that many clinicians are unaware of the potential contribution of pharmacogenetic testing and have not implemented this new modality in their daily practice. We present a case of Stevens-Johnson syndrome in a patient treated with carbamazepine. Following the pathways of clinical reasoning, we describe the possibilities of pharmacogenetic testing in the clinic (HLA-B1502 and HLA-A3101 in our patient). We describe the pharmacological and pharmacogenetic aspects relevant for the clinician's daily practice (the existence of ADR subtypes, cytochrome P450, drug-drug interactions, genetic variations, CYP450 and HLA genotyping). Based on the Dutch top 100 of most prescribed drugs, we provide data on CYP450 and HLA genotypes relevant to those 100 most commonly used drugs. We discuss the availability and costs of pharmacogenetic testing, show a calculation of the 'number needed to genotype' and, based on these data, we propose a decision model for pharmacogenetic testing by clinicians.
考虑到临床中药物不良反应（ADR）的高发性，以及对某些ADR潜在遗传机制的认识不断增加，我们认为每位临床医生至少应了解药物遗传学的基本原理。然而，我们的经验是，许多临床医生并未意识到药物遗传学检测的潜在作用，也未在日常实践中采用这种新方法。我们报告一例使用卡马西平治疗的患者发生史蒂文斯-约翰逊综合征的病例。按照临床推理路径，我们描述了临床中进行药物遗传学检测的可能性（我们的患者检测了HLA-B1502和HLA-A3101）。我们描述了与临床医生日常实践相关的药理学和药物遗传学方面（ADR亚型的存在、细胞色素P450、药物相互作用、基因变异、CYP450和HLA基因分型）。基于荷兰最常用的100种药物，我们提供了与这100种最常用药物相关的CYP450和HLA基因型数据。我们讨论了药物遗传学检测的可及性和成本，展示了“基因分型所需数量”的计算，并基于这些数据，为临床医生提出了一个药物遗传学检测决策模型。
