{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:37:36Z","timestamp":1780601856589,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["483714\/2013\u20105"],"award-info":[{"award-number":["483714\/2013\u20105"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in <jats:italic>BMP6<\/jats:italic> (rs3812163, rs270393 and rs449853) and <jats:italic>VDR<\/jats:italic> (<jats:italic>FokI<\/jats:italic> rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of <jats:italic>BMP6<\/jats:italic> rs3812163 was independently associated with a lower osteonecrosis risk (<jats:italic>p<\/jats:italic>\u2009=\u20090.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18\u20130.83) and with the long\u2010term cumulative incidence of osteonecrosis (<jats:italic>p<\/jats:italic>\u2009=\u20090.029; hazard ratio: 0.56, 95% CI: 0.34\u20130.94). The <jats:italic>VDR<\/jats:italic> rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (<jats:italic>p<\/jats:italic>\u2009=\u20090.039; OR: 0.14; 95% CI: 0.02\u20130.90). In summary, our results provide evidence that <jats:italic>BMP6<\/jats:italic> rs3812163 and the <jats:italic>VDR<\/jats:italic> rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.<\/jats:p>","DOI":"10.1111\/bjh.19329","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T09:49:31Z","timestamp":1707299371000},"page":"1507-1514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>BMP6<\/i> and <i>VDR<\/i> gene polymorphisms are associated with osteonecrosis in a sickle cell anaemia cohort"],"prefix":"10.1111","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1736-0227","authenticated-orcid":false,"given":"Gabriela S.","family":"Arcanjo","sequence":"first","affiliation":[{"name":"Genetics Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana B.","family":"Souza","sequence":"additional","affiliation":[{"name":"Genetics Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor F.","family":"Domingos","sequence":"additional","affiliation":[{"name":"Pronto Socorro Cardiol\u00f3gico de Pernambuco University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-4311","authenticated-orcid":false,"given":"Diego A.","family":"Pereira\u2010Martins","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cancer Research Centre Groningen University Medical Centre Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego A.","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"Genetics Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica V.","family":"Batista","sequence":"additional","affiliation":[{"name":"Genetics Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betania L.","family":"Hatzlhofer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madi V.","family":"Diniz","sequence":"additional","affiliation":[{"name":"Genetics Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexsandro P.","family":"Silva","sequence":"additional","affiliation":[{"name":"Genetics Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werbson L.","family":"Guaran\u00e1","sequence":"additional","affiliation":[{"name":"Genetics Postgraduate Program Federal University of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela F.","family":"Hazin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hematology and Hemotherapy Foundation of Pernambuco  Recife Pernambuco Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aderson S.","family":"Araujo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hematology and Hemotherapy Foundation of Pernambuco  Recife Pernambuco 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