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dc.creatorBarba E., Kontou P.I., Michalopoulos I., Bagos P.G., Braliou G.G.en
dc.date.accessioned2023-01-31T07:35:58Z
dc.date.available2023-01-31T07:35:58Z
dc.date.issued2022
dc.identifier10.1038/s41397-021-00255-3
dc.identifier.issn1470269X
dc.identifier.urihttp://hdl.handle.net/11615/71122
dc.description.abstractAzathioprine (AZA) and its metabolite, mercaptopurine (6-MP), are widely used immunosuppressant drugs. Polymorphisms in genes implicated in AZA/6-MP metabolism, reportedly, could account in part for their potential toxicity. In the present study we performed a systematic review and a meta-analysis, comprising 30 studies and 3582 individuals, to investigate the putative genetic association of two inosine triphosphatase (ITPA) polymorphisms with adverse effects in patients treated with AZA/6-MP. We found that rs1127354 is associated with neutropenia in general populations and in children (OR: 2.39, 95%CI: 1.97–2.90, and OR: 2.43, 95%CI: 2.12–2.79, respectively), and with all adverse effects tested herein in adult populations (OR: 2.12, 95%CI: 1.22–3.69). We also found that rs7270101 is associated with neutropenia and leucopenia in all-ages populations (OR: 2.93, 95%CI: 2.36–3.63, and OR: 2.82, 95%CI: 1.76–4.50, respectively) and with all adverse effects tested herein in children (OR: 1.74, 95%CI: 1.06–2.87). Stratification according to background disease, in combination with multiple comparisons corrections, verified neutropenia to be associated with both polymorphisms, in acute lymphoblastic leukemia (ALL) patients. These findings suggest that ITPA polymorphisms could be used as predictive biomarkers for adverse effects of thiopurine drugs to eliminate intolerance in ALL patients and clarify dosing in patients with different ITPA variants. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.en
dc.language.isoenen
dc.sourcePharmacogenomics Journalen
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85122894409&doi=10.1038%2fs41397-021-00255-3&partnerID=40&md5=8cfc96beefee5e6bb72f5b0bdd58b20f
dc.subjectazathioprineen
dc.subjectmercaptopurineen
dc.subjectazathioprineen
dc.subjectimmunosuppressive agenten
dc.subjectinorganic pyrophosphataseen
dc.subjectITPA protein, humanen
dc.subjectmercaptopurineen
dc.subjectacute lymphoblastic leukemiaen
dc.subjectadverse drug reactionen
dc.subjectageen
dc.subjectalopeciaen
dc.subjectArticleen
dc.subjectbone marrow suppressionen
dc.subjectcancer patienten
dc.subjectdisease markeren
dc.subjectDNA polymorphismen
dc.subjectdrug hypersensitivityen
dc.subjectflu like syndromeen
dc.subjectgeneen
dc.subjectgenetic associationen
dc.subjecthumanen
dc.subjectITPA geneen
dc.subjectleukopeniaen
dc.subjectliver toxicityen
dc.subjectmeta analysisen
dc.subjectnausea and vomitingen
dc.subjectneutropeniaen
dc.subjectpancreatitisen
dc.subjectpatienten
dc.subjectpediatric patienten
dc.subjectpharmacogeneticsen
dc.subjectpredictionen
dc.subjectPreferred Reporting Items for Systematic Reviews and Meta-Analysesen
dc.subjectrashen
dc.subjectside effecten
dc.subjectskin manifestationen
dc.subjectsystematic reviewen
dc.subjectgenetic polymorphismen
dc.subjectgeneticsen
dc.subjectAzathioprineen
dc.subjectHumansen
dc.subjectImmunosuppressive Agentsen
dc.subjectMercaptopurineen
dc.subjectPolymorphism, Geneticen
dc.subjectPyrophosphatasesen
dc.subjectSpringer Natureen
dc.titleAssociation of ITPA gene polymorphisms with adverse effects of AZA/6-MP administration: a systematic review and meta-analysisen
dc.typejournalArticleen


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