{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:19:50Z","timestamp":1792113590603,"version":"4.4.0"},"reference-count":115,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ADOPTION (FOE, Project \u2018Nuovi Biomarker Diagnostici e Terapeutici delle Malattie Neurodegenerative\u2019)","award":["CNR CUP:B83C21001810005"],"award-info":[{"award-number":["CNR CUP:B83C21001810005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The flavoenzyme N-ribosyldihydronicotinamide (NRH):quinone oxidoreductase 2 (NQO2) catalyzes two-electron reductions of quinones. NQO2 contributes to the metabolism of biogenic and xenobiotic quinones, including a wide range of antitumor drugs, with both toxifying and detoxifying functions. Moreover, NQO2 activity can be inhibited by several compounds, including drugs and phytochemicals such as flavonoids. NQO2 may play important roles that go beyond quinone metabolism and include the regulation of oxidative stress, inflammation, and autophagy, with implications in carcinogenesis and neurodegeneration. NQO2 is a highly polymorphic gene with several allelic variants, including insertions (I), deletions (D) and single-nucleotide (SNP) polymorphisms located mainly in the promoter, but also in other regulatory regions and exons. This is the first systematic review of the literature reporting on NQO2 gene variants as risk factors in degenerative diseases or drug adverse effects. In particular, hypomorphic 29 bp I alleles have been linked to breast and other solid cancer susceptibility as well as to interindividual variability in response to chemotherapy. On the other hand, hypermorphic polymorphisms were associated with Parkinson\u2019s and Alzheimer\u2019s disease. The I and D promoter variants and other NQO2 polymorphisms may impact cognitive decline, alcoholism and toxicity of several nervous system drugs. Future studies are required to fill several gaps in NQO2 research.<\/jats:p>","DOI":"10.3390\/genes15010087","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T09:39:57Z","timestamp":1704879597000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Polymorphisms and Pharmacogenomics of NQO2: The Past and the Future"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6787-7291","authenticated-orcid":false,"given":"Elzbieta","family":"Janda","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Toxicology, Department of Health Science, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0068-7204","authenticated-orcid":false,"given":"Jean A.","family":"Boutin","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroendocrine Endocrine and Germinal Differentiation and Communication (NorDiC), Universit\u00e9 de Rouen Normandie, INSERM, UMR 1239, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"De Lorenzo","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Toxicology, Department of Health Science, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8387-3664","authenticated-orcid":false,"given":"Mariamena","family":"Arbitrio","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1124\/molpharm.120.000105","article-title":"Molecular Pharmacology of NRH:Quinone Oxidoreductase 2: A Detoxifying Enzyme Acting as an Undercover Toxifying Enzyme","volume":"98","author":"Janda","year":"2020","journal-title":"Mol. 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