{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:14:19Z","timestamp":1788797659936,"version":"build-2803163510"},"reference-count":219,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Heme oxygenase (HO) metabolizes heme into ferrous iron, carbon monoxide (CO), and biliverdin-IX\u03b1 (BV), the latter being reduced into bilirubin-IX\u03b1 (BR) by the biliverdin reductase-A (BVR). Heme oxygenase exists as two isoforms, HO-1, inducible and involved in the cell stress response, and HO-2, constitutive and committed to the physiologic turnover of heme and in the intracellular oxygen sensing. Many studies have identified genetic variants of the HO\/BVR system and suggested their connection in free radical-induced diseases. The most common genetic variants include (GT)n dinucleotide length polymorphisms and single nucleotide polymorphisms. Gain-of-function mutations in the HO-1 and HO-2 genes foster the ventilator response to hypoxia and reduce the risk of coronary heart disease and age-related macular degeneration but increase the risk of neonatal jaundice, sickle cell disease, and Parkinson\u2019s disease. Conversely, loss-of-function mutations in the HO-1 gene increase the risk of type 2 diabetes mellitus, chronic obstructive pulmonary disease, and some types of cancers. Regarding BVR, the reported loss-of-function mutations increase the risk of green jaundice. Unfortunately, the physiological role of the HO\/BVR system does not allow for the hypothesis gene silencing\/induction strategies, but knowledge of these mutations can certainly facilitate a medical approach that enables early diagnoses and tailored treatments.<\/jats:p>","DOI":"10.3390\/antiox14020187","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T04:47:31Z","timestamp":1738817251000},"page":"187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Heme Oxygenase\/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases"],"prefix":"10.3390","volume":"14","author":[{"given":"Cesare","family":"Mancuso","sequence":"first","affiliation":[{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo F. Vito, 1, 00168 Rome, Italy"},{"name":"Department of Healthcare Surveillance and Bioethics, Section of Pharmacology, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito, 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6388","DOI":"10.1016\/S0021-9258(18)63477-5","article-title":"Microsomal heme oxygenase. Characterization of the enzyme","volume":"244","author":"Tenhunen","year":"1969","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mancuso, C. (2023). The impact of heme oxygenase-2 on pharmacological research: A bibliometric analysis and beyond. Front. 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