甲氨蝶呤遗传药理学的研究进展

发布时间：2018-03-26 00:47

本文选题：甲氨蝶呤　切入点：基因多态性　出处：《中国药房》2017年02期

【摘要】：目的:了解甲氨蝶呤(MTX)的遗传药理学研究进展。方法:查阅近年来国内外相关文献,就MTX遗传药理学的研究进展进行归纳和总结。结果与结论:MTX不能自由跨过细胞膜,须借助还原性叶酸载体1进入胞内发挥药理作用;细胞上的三磷酸腺苷结合盒转运体可将进入胞内的MTX转出细胞;有机阴离子转运肽介导两亲性物质的摄取,上述转运体基因多态性会影响MTX的疗效。多聚谷氨酰胺合成酶、γ-谷氨酰水解酶、二氢叶酸还原酶、亚甲基四氢叶酸还原酶(MTHFR)、胸苷酸合成酶、5-氨基咪唑-4-甲酰胺-核苷酸甲酰转移酶、蛋氨酸合成酶和蛋氨酸合成还原酶等的基因多态性会直接影响MTX的代谢、疗效和不良反应。目前能够用于临床的基因多态性位点仅为MTHFR 677CT和MTHFR 1298AC,可通过筛查其单核苷酸基因多态性来指导非霍奇金淋巴瘤患者的大剂量MTX化疗。MTX的作用受多种基因及其相互作用调控,可能还存在种族等其他因素作用,需对与MTX相关的基因多态性位点进行更深入的综合研究。
[Abstract]:Objective: to understand the progress of genetic pharmacology of methotrexate (MTX). Methods: the research progress of MTX genetic pharmacology was summarized and summarized by referring to the related literatures at home and abroad in recent years. It is necessary to use reductive folic acid vector 1 to play a pharmacological role; adenosine triphosphate binding box transporter on cells can transfer MTX into cells; organic anion transport peptide mediates the uptake of amphiphilic substances. Polyglutamine synthase, 纬 -glutamyl hydrolase, dihydrofolate reductase, polyglutamine synthase, dihydrofolate reductase, The polymorphisms of methylene tetrahydrofolate reductase (MTHFR), thymidylate synthase (thymidazole-4-formyltransferase), methionine synthase (Met) and methionine synthase (Met) directly affect the metabolism of MTX. Efficacy and adverse reactions. At present, MTHFR 677CT and MTHFR 1298ACare the only gene polymorphisms that can be used in clinic. It can be used to screen the single nucleotide polymorphisms to guide the high-dose MTX chemotherapy .MTX in patients with non-Hodgkin 's lymphoma. Regulation of multiple genes and their interactions, There may also be other factors, such as race, that require a more comprehensive study of genetic polymorphisms associated with MTX.
【作者单位】：武汉大学中南医院临床药学室;
【分类号】：R968

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