Department of Clinical Pharmacology, University Medical Center, Göttingen, Germany.
Pathology. 2012 Feb;44(2):166-80. doi: 10.1097/PAT.0b013e32834f4d69.
Pharmacogenetics has substantially added to our understanding of the variability of drug response. A number of single gene markers have been established and are ready to use in clinical practice. Here we review the validity and utility of markers in a number of genes (CYP2D6, CYP2C19, CYP2C9, VKORC1, TPMT, UGT1A1, OATP1B1, KRAS and HLA locus) for therapy decisions. As drug response is a complex trait in the majority of cases, most of the identified functional variants will only explain a limited part of the variability of drug response. In this sense, a phenotype is the product of many low-penetrance variations. Technical progress has not only improved the cost-effectiveness of screening for single gene markers, but offers the possibility of generating vast amounts of genome-wide single nucleotide polymorphism (SNP) or sequence data for each patient. The latest challenge is to incorporate these amounts of data into pharmacogenetic decision support. We discuss here the challenges associated with choosing the correct therapy for patients who present to their physicians with personal genome data.
药物遗传学在很大程度上增加了我们对药物反应可变性的理解。已经确定了许多单基因标记物，并且已经准备好在临床实践中使用。在这里，我们回顾了一些基因（CYP2D6、CYP2C19、CYP2C9、VKORC1、TPMT、UGT1A1、OATP1B1、KRAS 和 HLA 基因座）中标记物在治疗决策中的有效性和实用性。由于药物反应在大多数情况下是一种复杂的特征，因此大多数已识别的功能变体仅能解释药物反应可变性的有限部分。从这个意义上说，表型是许多低外显率变异的产物。技术进步不仅提高了筛选单基因标记物的成本效益，而且还为每位患者生成大量全基因组单核苷酸多态性（SNP）或序列数据提供了可能性。最新的挑战是将这些数据量纳入药物遗传学决策支持中。我们在这里讨论了与为向医生提供个人基因组数据的患者选择正确治疗方法相关的挑战。
