Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor‐1 and osteonecrosis risk in childhood acute lymphoblastic leukemia

Abstract Background Osteonecrosis (ON) is one of the major therapy‐related 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 pl...

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Main Authors: Laila M. Sherief, Mohamed Beshir, Nermin Raafat, Elhamy R. Abdelkhalek, Wesam A. Mokhtar, Khaled M. Elgerby, Basma K. Soliman, Hosam E. Salah, Ghada A. Mokhtar, Naglaa M. Kamal, Heba ELsayed, Marwa Zakaria
Format: Article
Language:English
Published: Wiley 2021-07-01
Series:Molecular Genetics & Genomic Medicine
Subjects:
Online Access:https://doi.org/10.1002/mgg3.1700
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author Laila M. Sherief
Mohamed Beshir
Nermin Raafat
Elhamy R. Abdelkhalek
Wesam A. Mokhtar
Khaled M. Elgerby
Basma K. Soliman
Hosam E. Salah
Ghada A. Mokhtar
Naglaa M. Kamal
Heba ELsayed
Marwa Zakaria
author_facet Laila M. Sherief
Mohamed Beshir
Nermin Raafat
Elhamy R. Abdelkhalek
Wesam A. Mokhtar
Khaled M. Elgerby
Basma K. Soliman
Hosam E. Salah
Ghada A. Mokhtar
Naglaa M. Kamal
Heba ELsayed
Marwa Zakaria
author_sort Laila M. Sherief
collection DOAJ
description Abstract Background Osteonecrosis (ON) is one of the major therapy‐related 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‐1 (PAI‐1) gene can affect the risk of ON. Patients and Methods Nighty‐six ALL children were enrolled. Serum 25‐hydroxyvitamin D 25(OH)D levels were performed in addition to the detection of polymorphisms in PAI‐1and VDR genes by polymerase chain reaction. Results Ten out of 96 patients had ON (four males and six females aged above 10 years) and had an insufficient level of 25(OH)D. Fifty‐two percent of patients had PAI‐1 GG genotype while 48% had PAI‐1 GA genotype. PAI‐1 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. Conclusion 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‐1 and VDR gene polymorphism may be a genetic risk factor in its pathogenesis.
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spelling doaj.art-50185a15b44e4cadad9f68749736c8e12022-12-21T22:33:26ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-07-0197n/an/a10.1002/mgg3.1700Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor‐1 and osteonecrosis risk in childhood acute lymphoblastic leukemiaLaila M. Sherief0Mohamed Beshir1Nermin Raafat2Elhamy R. Abdelkhalek3Wesam A. Mokhtar4Khaled M. Elgerby5Basma K. Soliman6Hosam E. Salah7Ghada A. Mokhtar8Naglaa M. Kamal9Heba ELsayed10Marwa Zakaria11Department of Pediatrics Faculty of Medicine Zagazig University Zagazig EgyptDepartment of Pediatrics Faculty of Medicine Zagazig University Zagazig EgyptDepartment of Medical Biochemistry Faculty of Medicine Zagazig University Zagazig EgyptDepartment of Pediatrics Faculty of Medicine Zagazig University Zagazig EgyptDepartment of Pediatrics Faculty of Medicine Zagazig University Zagazig EgyptDepartment of Radiodiagnosis Faculty of Medicine Zagazig University Zagazig EgyptDepartment of Radiodiagnosis Faculty of Medicine Zagazig University Zagazig EgyptDepartment of Clinical Pathology Faculty of Medicine Zagazig University Zagazig EgyptDepartment of Medical Microbiology & Immunology Faculty of Medicine Zagazig University Zagazig EgyptPediatric Department Kasr Alainy Faculty of Medicine Cairo University Cairo EgyptDepartment of Pediatrics Faculty of Medicine Zagazig University Zagazig EgyptDepartment of Pediatrics Faculty of Medicine Zagazig University Zagazig EgyptAbstract Background Osteonecrosis (ON) is one of the major therapy‐related 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‐1 (PAI‐1) gene can affect the risk of ON. Patients and Methods Nighty‐six ALL children were enrolled. Serum 25‐hydroxyvitamin D 25(OH)D levels were performed in addition to the detection of polymorphisms in PAI‐1and VDR genes by polymerase chain reaction. Results Ten out of 96 patients had ON (four males and six females aged above 10 years) and had an insufficient level of 25(OH)D. Fifty‐two percent of patients had PAI‐1 GG genotype while 48% had PAI‐1 GA genotype. PAI‐1 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. Conclusion 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‐1 and VDR gene polymorphism may be a genetic risk factor in its pathogenesis.https://doi.org/10.1002/mgg3.1700ALLosteonecrosisPAI‐1pediatricpolymorphismVDR
spellingShingle Laila M. Sherief
Mohamed Beshir
Nermin Raafat
Elhamy R. Abdelkhalek
Wesam A. Mokhtar
Khaled M. Elgerby
Basma K. Soliman
Hosam E. Salah
Ghada A. Mokhtar
Naglaa M. Kamal
Heba ELsayed
Marwa Zakaria
Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor‐1 and osteonecrosis risk in childhood acute lymphoblastic leukemia
Molecular Genetics & Genomic Medicine
ALL
osteonecrosis
PAI‐1
pediatric
polymorphism
VDR
title Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor‐1 and osteonecrosis risk in childhood acute lymphoblastic leukemia
title_full Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor‐1 and osteonecrosis risk in childhood acute lymphoblastic leukemia
title_fullStr Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor‐1 and osteonecrosis risk in childhood acute lymphoblastic leukemia
title_full_unstemmed Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor‐1 and osteonecrosis risk in childhood acute lymphoblastic leukemia
title_short Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor‐1 and osteonecrosis risk in childhood acute lymphoblastic leukemia
title_sort genetic polymorphism of vitamin d receptors and plasminogen activator inhibitor 1 and osteonecrosis risk in childhood acute lymphoblastic leukemia
topic ALL
osteonecrosis
PAI‐1
pediatric
polymorphism
VDR
url https://doi.org/10.1002/mgg3.1700
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