{"title":"The effects of genetic polymorphism on toxicity and pharmacokinetics of methotrexate in Egyptian adult patients with leukaemia or lymphoma.","authors":"Khloud Shendy, Khaled Abdelkawy, Ahmed Amin Ali, Fathalla Belal, Mostafa Abdelhakiem, Galal Magdy, Nahla Anber, Fawzy Elbarbry","doi":"10.1080/00498254.2024.2320778","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"95-105"},"PeriodicalIF":1.3000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Xenobiotica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00498254.2024.2320778","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/5 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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
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