The Outlier in All of Us: Why Implementing Pharmacogenomics Could Matter for Everyone.
The Outlier in All of Us: Why Implementing Pharmacogenomics Could Matter for Everyone.
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DOI：
10.1002/cpt.333
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发表时间：
2016-04
影响因子：
6.7
通讯作者：
Ratain MJ
中科院分区：
文献类型：
--
作者：
O'Donnell PH;Danahey K;Ratain MJ
药物基因组学领域最初出现于20世纪50年代，当时观察到少数罕见的个体对药物有意想不到的严重反应。就在六年前，关于这个问题的主要观点基本上没有改变，FDA的作者引用了药物遗传学的目的是“为离群值定制治疗”。如果这是流行的观点，那就不足为奇了--研究得最好的药物基因组学药物的例子确实就是这样，通常在很小一部分人群中对极端反应或敏感性的遗传解释。硫嘌呤甲基转移酶（TPMT）缺乏症是硫唑嘌呤或巯基嘌呤治疗后严重骨髓抑制的原因，仅在约10%的患者中发现杂合子特征，纯合子（缺乏症）携带者更罕见-发生在300例患者中不到1例。由吸入麻醉剂和琥珀酰胆碱引起的恶性高热据信具有仅约1/2000人的遗传发病率。
The field of pharmacogenomics originally emerged in the 1950s from observations that a few rare individuals had unexpected, severe reactions to drugs. As recently as just six years ago, prominent views on the subject had largely remained unchanged, with authors from the FDA citing the purpose of pharmacogenetics as “tailoring treatment for the outliers”. It should not be surprising if this is the prevailing view – the best-studied pharmacogenomic drug examples are indeed just that, genetic explanations of extreme responses or susceptibilities among usually a very small fraction of the human population. Thiopurine methyltransferase (TPMT) deficiency as a cause of severe myelosuppression upon treatment with azathioprine or mercaptopurine is found as a heterozygous trait in only approximately 10% of patients, and homozygous (deficiency) carriers are even more rare – occurring in fewer than 1 in 300 patients. Malignant hyperthermia resulting from inhaled anesthetics and succinylcholine is believed to have a genetic incidence of only about 1 in 2000 people.