Department of Neuroscience, Unit of Pharmacology, School of Medicine, University Politecnica delle Marche, Ancona, Italy.
Curr Drug Metab. 2011 Mar;12(3):278-86. doi: 10.2174/138920011795101840.
It is well known that interindividual variability can affect the response to many drugs in relation to age, gender, diet, and organ function. Pharmacogenomic studies have also documented that genetic polymorphisms can exert clinically significant effects in terms of drug resistance, efficacy and toxicity by modifying the expression of critical gene products (drug-metabolizing enzymes, transporters, and target molecules) as well as pharmacokinetic and pharmacodynamic parameters. A growing body of in vitro and clinical evidence suggests that common polymorphisms in the folate gene pathway are associated with an altered response to methotrexate (MTX) in patients with malignancy and autoimmune disease. Such polymorphisms may also induce significant MTX toxicity requiring expensive monitoring and treatment. Although the available data are not conclusive, they suggest that in the future MTX pharmacogenetics could play a key role in clinical practice by improving and tailoring treatment. This review describes the genetic polymorphisms that significantly influence MTX resistance, efficacy, and toxicity.
众所周知，个体间的差异会影响许多药物的反应，这与年龄、性别、饮食和器官功能有关。药物基因组学研究还记录了遗传多态性可以通过改变关键基因产物（药物代谢酶、转运体和靶分子）的表达以及药代动力学和药效学参数，对药物耐药性、疗效和毒性产生临床显著影响。越来越多的体外和临床证据表明，叶酸基因途径中的常见多态性与恶性肿瘤和自身免疫性疾病患者对甲氨蝶呤（MTX）的反应改变有关。这种多态性也可能导致需要昂贵的监测和治疗的显著 MTX 毒性。尽管现有数据尚无定论，但它们表明，未来 MTX 药物遗传学可能通过改善和定制治疗在临床实践中发挥关键作用。这篇综述描述了显著影响 MTX 耐药性、疗效和毒性的遗传多态性。
