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Association of VDBP rs4701 Variant, but not VDR/RXR-α Over-Expression with Bone Mineral Density in Pediatric Well-Chelated β-Thalassemia Patients

BACKGROUND: The reduced rate of bone formation despite the availability of vitamin D has been reported in β-thalassemia. Genetic factors, together with environmental ones, could be implicated in this condition. Since vitamin D binding protein (VDBP) maintains bioavailability of vitamin D which binds...

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Autores principales: Sahmoud, Shaimaa, Ibrahim, Mostafa S., Toraih, Eman A., Kamel, Noha, Fawzy, Manal S., Elfiky, Samar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Università Cattolica del Sacro Cuore 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340238/
https://www.ncbi.nlm.nih.gov/pubmed/32670515
http://dx.doi.org/10.4084/MJHID.2020.037
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author Sahmoud, Shaimaa
Ibrahim, Mostafa S.
Toraih, Eman A.
Kamel, Noha
Fawzy, Manal S.
Elfiky, Samar
author_facet Sahmoud, Shaimaa
Ibrahim, Mostafa S.
Toraih, Eman A.
Kamel, Noha
Fawzy, Manal S.
Elfiky, Samar
author_sort Sahmoud, Shaimaa
collection PubMed
description BACKGROUND: The reduced rate of bone formation despite the availability of vitamin D has been reported in β-thalassemia. Genetic factors, together with environmental ones, could be implicated in this condition. Since vitamin D binding protein (VDBP) maintains bioavailability of vitamin D which binds to vitamin D receptor (VDR)-retinoid X receptor alpha (RXRA) heterodimer to exert its molecular actions, we speculated that vitamin D metabolic-axis expression signature and variants could be potential molecular candidates for bone turnover/disease in thalassemia. To this end, this study aims to analyze VDR/RXRA expression signature, and two VDBP variants in a pilot sample of Egyptian β-thalassemia children in correlation with bone mineral density (BMD). PATIENTS AND METHODS: Forty-four well-chelated β-thalassemia children and 40 unrelated controls were enrolled. The serum bone chemistry profile was measured. Peripheral blood mononuclear cells (PBMN) VDR/RXRA expression levels were quantified by Real-Time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). VDBP rs7041 and rs4588 variants were identified by Real-Time allelic discrimination assay. All patients were subjected to lumbar-spine Dual-energy X-ray absorptiometry (DEXA). RESULTS: VDR/RXRA expressions were significantly higher in β-thalassemia children compared to controls (P = 0.001 and <0.001, respectively) and showed higher values in β-thalassemia major relative to β-thalassemia intermedia. Expression levels of both genes were not associated with sex or BMD. However, VDBP rs4701 genotyping revealed lower BMD-L4 and a higher frequency of osteoporosis. CONCLUSIONS: β-Thalassemia children had higher expression levels of PBMN VDR/RXRA. VDBP rs4701 variant was associated with osteoporosis in our β-thalassemia patients on vitamin D supplementation. Further large-scale studies in other ethnic populations are warranted.
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spelling pubmed-73402382020-07-14 Association of VDBP rs4701 Variant, but not VDR/RXR-α Over-Expression with Bone Mineral Density in Pediatric Well-Chelated β-Thalassemia Patients Sahmoud, Shaimaa Ibrahim, Mostafa S. Toraih, Eman A. Kamel, Noha Fawzy, Manal S. Elfiky, Samar Mediterr J Hematol Infect Dis Original Article BACKGROUND: The reduced rate of bone formation despite the availability of vitamin D has been reported in β-thalassemia. Genetic factors, together with environmental ones, could be implicated in this condition. Since vitamin D binding protein (VDBP) maintains bioavailability of vitamin D which binds to vitamin D receptor (VDR)-retinoid X receptor alpha (RXRA) heterodimer to exert its molecular actions, we speculated that vitamin D metabolic-axis expression signature and variants could be potential molecular candidates for bone turnover/disease in thalassemia. To this end, this study aims to analyze VDR/RXRA expression signature, and two VDBP variants in a pilot sample of Egyptian β-thalassemia children in correlation with bone mineral density (BMD). PATIENTS AND METHODS: Forty-four well-chelated β-thalassemia children and 40 unrelated controls were enrolled. The serum bone chemistry profile was measured. Peripheral blood mononuclear cells (PBMN) VDR/RXRA expression levels were quantified by Real-Time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). VDBP rs7041 and rs4588 variants were identified by Real-Time allelic discrimination assay. All patients were subjected to lumbar-spine Dual-energy X-ray absorptiometry (DEXA). RESULTS: VDR/RXRA expressions were significantly higher in β-thalassemia children compared to controls (P = 0.001 and <0.001, respectively) and showed higher values in β-thalassemia major relative to β-thalassemia intermedia. Expression levels of both genes were not associated with sex or BMD. However, VDBP rs4701 genotyping revealed lower BMD-L4 and a higher frequency of osteoporosis. CONCLUSIONS: β-Thalassemia children had higher expression levels of PBMN VDR/RXRA. VDBP rs4701 variant was associated with osteoporosis in our β-thalassemia patients on vitamin D supplementation. Further large-scale studies in other ethnic populations are warranted. Università Cattolica del Sacro Cuore 2020-07-01 /pmc/articles/PMC7340238/ /pubmed/32670515 http://dx.doi.org/10.4084/MJHID.2020.037 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Sahmoud, Shaimaa
Ibrahim, Mostafa S.
Toraih, Eman A.
Kamel, Noha
Fawzy, Manal S.
Elfiky, Samar
Association of VDBP rs4701 Variant, but not VDR/RXR-α Over-Expression with Bone Mineral Density in Pediatric Well-Chelated β-Thalassemia Patients
title Association of VDBP rs4701 Variant, but not VDR/RXR-α Over-Expression with Bone Mineral Density in Pediatric Well-Chelated β-Thalassemia Patients
title_full Association of VDBP rs4701 Variant, but not VDR/RXR-α Over-Expression with Bone Mineral Density in Pediatric Well-Chelated β-Thalassemia Patients
title_fullStr Association of VDBP rs4701 Variant, but not VDR/RXR-α Over-Expression with Bone Mineral Density in Pediatric Well-Chelated β-Thalassemia Patients
title_full_unstemmed Association of VDBP rs4701 Variant, but not VDR/RXR-α Over-Expression with Bone Mineral Density in Pediatric Well-Chelated β-Thalassemia Patients
title_short Association of VDBP rs4701 Variant, but not VDR/RXR-α Over-Expression with Bone Mineral Density in Pediatric Well-Chelated β-Thalassemia Patients
title_sort association of vdbp rs4701 variant, but not vdr/rxr-α over-expression with bone mineral density in pediatric well-chelated β-thalassemia patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340238/
https://www.ncbi.nlm.nih.gov/pubmed/32670515
http://dx.doi.org/10.4084/MJHID.2020.037
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