The effects of genetic polymorphism on toxicity and pharmacokinetics of methotrexate in Egyptian adult patients with leukaemia or lymphoma.

IF 1.3 4区医学 Q4 PHARMACOLOGY & PHARMACY

Xenobiotica Pub Date : 2024-02-01 Epub Date: 2024-03-05 DOI:10.1080/00498254.2024.2320778

Khloud Shendy, Khaled Abdelkawy, Ahmed Amin Ali, Fathalla Belal, Mostafa Abdelhakiem, Galal Magdy, Nahla Anber, Fawzy Elbarbry

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引用次数: 0

Abstract

Polymorphisms in genes coding folate-metabolising enzymes might alter the pharmacokinetics and sensitivity for methotrexate "MTX".The aim of the study aimed to investigate the influence of MTHFR C677T, DHFR19 Ins/del, GGH -401 C > T, and MTR A2756G polymorphisms on MTX toxicity and pharmacokinetics in Egyptian patients with Acute lymphoblastic leukaemia (ALL) or Non-Hodgkin lymphoma (NHL).Fifty adult Egyptian patients with ALL and NHL, treated with high dose MTX, were prospectively enrolled in the study. Clinical and biochemical data was collected objectively from medical records after each cycle of MTX. Plasma concentrations of MTX were measured after 72 h of initiation of infusion. Genotyping was done with a PCR-ARMS and PCR-RFLP assays.The MTHFR C677T T variants significantly increased the risk of leukopoenia, whereas the genotype MTHFR 677 C > T TT significantly associated with lymphocytopenia, thrombocytopenia, and anaemia. The genotype GGH-401 TT was significantly correlated with anaemia. Plasma MTX level was significantly higher in patients with MTR A2756G G variants.MTHFR polymorphism played the main role in MTX toxicities. The pharmacokinetics of MTX was affected by MTR polymorphism. GGH mutation was mainly concerned with anaemia. Pharmacogenetic testing are recommended to optimise MTX therapy.

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埃及成人白血病或淋巴瘤患者基因多态性对甲氨蝶呤毒性和药代动力学的影响

1.叶酸代谢酶编码基因的多态性可能会改变甲氨蝶呤 "MTX "的药代动力学和敏感性。该研究旨在调查 MTHFR C677T、DHFR19 Ins/del、GGH -401 C > T 和 MTR A2756G 多态性对埃及急性淋巴细胞白血病（ALL）或非霍奇金淋巴瘤（NHL）患者 MTX 毒性和药代动力学的影响。 50 名接受大剂量 MTX 治疗的埃及成年 ALL 和 NHL 患者被纳入前瞻性研究。在每个 MTX 治疗周期结束后，从病历中客观收集临床和生化数据。开始输注后 72 小时测定 MTX 的血浆浓度。基因分型是通过 PCR-ARMS 和 PCR-RFLP 检测法进行的。 MTHFR C677T T 变体会显著增加白细胞减少症的风险，而基因型 MTHFR 677C > T TT 则与淋巴细胞减少症、血小板减少症和贫血症密切相关。基因型 GGH-401 TT 与贫血明显相关。MTR A2756G G 变体患者的血浆 MTX 水平明显更高。 MTHFR 多态性在 MTX 毒性中起主要作用。MTR多态性影响MTX的药代动力学。GGH 突变主要与贫血有关。建议进行药物基因检测，以优化MTX治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Xenobiotica 医学-毒理学

CiteScore

3.80

自引率

5.60%

发文量

审稿时长

2 months

期刊介绍： Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology