{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:16:30Z","timestamp":1779243390354,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Osteonecrosis (ON) is one of the major therapy\u2010related complications in childhood acute lymphoblastic leukemia (ALL). The purpose of the current study is to assess the frequency of ON in children with ALL and to detect whether polymorphisms in vitamin D receptor gene (VDR) and plasminogen activator inhibitor\u20101 (PAI\u20101) gene can affect the risk of ON.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>Nighty\u2010six ALL children were enrolled. Serum 25\u2010hydroxyvitamin D 25(OH)D levels were performed in addition to the detection of polymorphisms in PAI\u20101and VDR genes by polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten out of 96 patients had ON (four males and six females aged above 10\u00a0years) and had an insufficient level of 25(OH)D. Fifty\u2010two percent of patients had PAI\u20101 GG genotype while 48% had PAI\u20101 GA genotype. PAI\u20101 polymorphism was detected in 60% of all ON cases. The frequencies of VDR genotypes were CT (56.3%), CC (39.6%), and TT (4.2%). Osteonecrosis was found in eight patients with CC genotype and in two patients with CT genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Osteonecrosis can develop early during the therapy of ALL. Older age and insufficient level of 25(OH)D were considered important risk factor for the development of osteonecrosis. PAT\u20101 and VDR gene polymorphism may be a genetic risk factor in its pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1700","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T11:42:47Z","timestamp":1622115767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor\u20101 and osteonecrosis risk in childhood acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"9","author":[{"given":"Laila M.","family":"Sherief","sequence":"first","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Beshir","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nermin","family":"Raafat","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elhamy R.","family":"Abdelkhalek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wesam A.","family":"Mokhtar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaled M.","family":"Elgerby","sequence":"additional","affiliation":[{"name":"Department of Radiodiagnosis Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basma K.","family":"Soliman","sequence":"additional","affiliation":[{"name":"Department of Radiodiagnosis Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hosam E.","family":"Salah","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghada A.","family":"Mokhtar","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8535-3838","authenticated-orcid":false,"given":"Naglaa M.","family":"Kamal","sequence":"additional","affiliation":[{"name":"Pediatric Department Kasr Alainy Faculty of Medicine Cairo University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heba","family":"ELsayed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa","family":"Zakaria","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"747","article-title":"Osteonecrosis: An emerging complication of intensive chemotherapy for childhood acute lymphoblastic leukemia","volume":"88","author":"Aric\u00f2 M.","year":"2003","journal-title":"Hematologiaca"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000101433.99651.96"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21405"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-355206"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2018.02.006"},{"key":"e_1_2_13_7_1","first-page":"505","article-title":"Pharmacogenetics of the vitamin D receptor and osteoporosis","volume":"29","author":"Eisman J. 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