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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Università Cattolica del Sacro Cuore
2020
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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. |
format | Online Article Text |
id | pubmed-7340238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Università Cattolica del Sacro Cuore |
record_format | MEDLINE/PubMed |
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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