BMP6 and VDR gene polymorphisms are associated with osteonecrosis in a sickle cell anaemia cohort.

Autor: Arcanjo GS; Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Souza MB; Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Domingos IF; Pronto Socorro Cardiológico de Pernambuco, University of Pernambuco, Recife, Pernambuco, Brazil., Pereira-Martins DA; Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands., Falcão DA; Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Batista JV; Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Hatzlhofer BL; Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Diniz MV; Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Silva AP; Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Guaraná WL; Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Hazin MF; Department of Internal Medicine, Hematology and Hemotherapy Foundation of Pernambuco, Recife, Pernambuco, Brazil., Araujo AS; Department of Internal Medicine, Hematology and Hemotherapy Foundation of Pernambuco, Recife, Pernambuco, Brazil., Cunha AF; Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, São Paulo, Brazil., Saad SO; Hematology and Hemotherapy Center, State University of Campinas, Campinas, São Paulo, Brazil., Costa FF; Hematology and Hemotherapy Center, State University of Campinas, Campinas, São Paulo, Brazil., Lucena-Araujo AR; Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Pernambuco, Brazil., Bezerra MAC; Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Pernambuco, Brazil.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2024 Apr; Vol. 204 (4), pp. 1507-1514. Date of Electronic Publication: 2024 Feb 07.
DOI: 10.1111/bjh.19329
Abstrakt: 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 BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI 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 BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18-0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34-0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02-0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.
(© 2024 British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: