Original Articles
Vol. 11 No. 1 (2019): Review Articles, Original Articles, Scientific Letters, Case Reports, Letters to Editor.
BONE MINERAL DENSITY AND VITAMIN D RECEPTOR GENETIC VARIANTS IN EGYPTIAN CHILDREN WITH BETA THALASSEMIA ON VITAMIN D SUPPLEMENTATION
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: August 9, 2018
Accepted: November 26, 2018
Accepted: November 26, 2018
2379
Views
1183
Downloads
200
HTML
Hematology
Authors
Background: Low bone mineral density (BMD) is a characteristic feature of Beta thalassemia major (?TM) patients. Vitamin D is important for bone mineralization. Vitamin D receptors (VDR) genetic variants may be related to vitamin D status and BMD.
Objectives: To evaluate the effect of VDR genetic variants on vitamin D levels and BMD in ?TM Egyptian patients supplemented with vitamin D.
Methods: This study was conducted on forty children with ?TM and forty unrelated healthy sex and age-matched controls. Serum calcium, phosphorus, ALP, ferritin and vitamin D were measured. VDR genetic variants (BsmI, TaqI, and FokI) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). BMD was measured by dual-energy X-ray densitometry (DEXA) of the lumbar spine.
Results: In ?TM patients, 22.5% had deficient, 50% had insufficient and only 27.5% had sufficient levels of vitamin D. BMD Z score was significantly lower in ?TM patients compared to controls (p<0.001). Osteopenia and osteoporosis of lumbar spines were observed in 70% and 22.5% of ?TM patients respectively. BsmI bb and FokI Ff and ff genotypic variants were significantly associated with lower vitamin D and BMD Z score. No association was observed with TaqI genotypic variants.
Conclusions: We reported a high prevalence of low BMD in ?TM despite vitamin D supplementation. The BsmI bb, FokI Ff and ff genotypic variants of VDR can be considered as risk factors for the occurrence of osteoporosis in these children. Vitamin D doses should be adjusted individually according to the genetic makeup of each patient.
Downloads
Download data is not yet available.
Citations
Higgs DR, Engel JD, Stamatoyannopoulos G: Thalassaemia. Lancet 2012, 379(9813):373-383.http://www.ncbi.nlm.nih.gov/pubmed/21908035
El-Shanshory M, Hagag A, Shebl S, Badria I, Abd Elhameed A, Abd El-Bar E, Al-Tonbary Y, Mansour A, Hassab H, Hamdy M, Alfy M, Sherief L, Sharaf E: Spectrum of Beta Globin Gene Mutations in Egyptian Children with beta-Thalassemia. Mediterr J Hematol Infect Dis 2014, 6(1):e2014071.http://www.ncbi.nlm.nih.gov/pubmed/25408857
Kesse-Adu R, Howard J: Inherited anaemias: sickle cell and thalassaemia. Medicine, 41(4):219-224.http://dx.doi.org/10.1016/j.mpmed.2013.01.012
Voskaridou E, Terpos E: New insights into the pathophysiology and management of osteoporosis in patients with beta thalassaemia. Br J Haematol 2004, 127(2):127-139.http://www.ncbi.nlm.nih.gov/pubmed/15461618
Borgna-Pignatti C, Gamberini MR: Complications of thalassemia major and their treatment. Expert Rev Hematol 2011, 4(3):353-366.http://www.ncbi.nlm.nih.gov/pubmed/21668399
Soliman A, Adel A, Wagdy M, Al Ali M, ElMulla N: Calcium homeostasis in 40 adolescents with beta-thalassemia major: a case-control study of the effects of intramuscular injection of a megadose of cholecalciferol. Pediatr Endocrinol Rev 2008, 6 Suppl 1:149-154.http://www.ncbi.nlm.nih.gov/pubmed/19337170
Sunyecz JA: The use of calcium and vitamin D in the management of osteoporosis. Ther Clin Risk Manag 2008, 4(4):827-836.http://www.ncbi.nlm.nih.gov/pubmed/19209265
Laczmanska I, Laczmanski L, Bebenek M, Karpinski P, Czemarmazowicz H, Ramsey D, Milewicz A, Sasiadek MM: Vitamin D receptor gene polymorphisms in relation to the risk of colorectal cancer in the Polish population. Tumour Biol 2014, 35(12):12397-12401.http://www.ncbi.nlm.nih.gov/pubmed/25195132
Abu Shady MM, Youssef MM, Salah El-Din EM, Abdel Samie OM, Megahed HS, Salem SM, Mohsen MA, Abdel Aziz A, El-Toukhy S: Predictors of Serum 25-Hydroxyvitamin D Concentrations among a Sample of Egyptian Schoolchildren. ScientificWorldJournal 2016, 2016:8175768.http://www.ncbi.nlm.nih.gov/pubmed/26942211
Zhang L, Yin X, Wang J, Xu D, Wang Y, Yang J, Tao Y, Zhang S, Feng X, Yan C: Associations between VDR Gene Polymorphisms and Osteoporosis Risk and Bone Mineral Density in Postmenopausal Women: A systematic review and Meta-Analysis. Sci Rep 2018, 8(1):981.http://www.ncbi.nlm.nih.gov/pubmed/29343720
Singh K, Kumar R, Shukla A, Phadke SR, Agarwal S: Status of 25-hydroxyvitamin D deficiency and effect of vitamin D receptor gene polymorphisms on bone mineral density in thalassemia patients of North India. Hematology 2012, 17(5):291-296.http://www.ncbi.nlm.nih.gov/pubmed/22971535
El-Edel RH, Ghonaim MM, Abo-Salem OM, El-Nemr FM: Bone mineral density and vitamin D receptor polymorphism in beta-thalassemia major. Pak J Pharm Sci 2010, 23(1):89-96.http://www.ncbi.nlm.nih.gov/pubmed/20067873
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM: Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011, 96(7):1911-1930.http://www.ncbi.nlm.nih.gov/pubmed/21646368
Bid HK, Konwar R, Aggarwal CG, Gautam S, Saxena M, Nayak VL, Banerjee M: Vitamin D receptor (FokI, BsmI and TaqI) gene polymorphisms and type 2 diabetes mellitus: a North Indian study. Indian J Med Sci 2009, 63(5):187-194.http://www.ncbi.nlm.nih.gov/pubmed/19584489
Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 1994, 843:1-129.http://www.ncbi.nlm.nih.gov/pubmed/7941614
Bikle DD: Vitamin D and bone. Curr Osteoporos Rep 2012, 10(2):151-159.http://www.ncbi.nlm.nih.gov/pubmed/22544628
Soliman A, De Sanctis V, Yassin M: Vitamin d status in thalassemia major: an update. Mediterr J Hematol Infect Dis 2013, 5(1):e2013057.http://www.ncbi.nlm.nih.gov/pubmed/24106607
Shady MM, Youssef MM, Shehata MA, El-Din EM, ElMalt HA: Association of Serum 25-Hydroxyvitamin D with Life Style and Dietary Factors in Egyptian Prepubescent Children. Open Access Maced J Med Sci 2015, 3(1):80-84.http://www.ncbi.nlm.nih.gov/pubmed/27275201
El Badawy AA, Aboserea MM, El Seifi OS, Mortada EM, Bakry HM, Waly EH, Raafat N, Etewa RL, El Badawy SA: Vitamin D, Parathormone and Associated Minerals among Students in Zagazig District, Sharkia Governorate, Egypt. Int J Vitam Nutr Res 2014, 84(3-4):173-182.http://www.ncbi.nlm.nih.gov/pubmed/26098481
Elhoseiny SM, Morgan DS, Rabie AM, Bishay ST: Vitamin D Receptor (VDR) Gene Polymorphisms (FokI, BsmI) and their Relation to Vitamin D Status in Pediatrics betaeta Thalassemia Major. Indian J Hematol Blood Transfus 2016, 32(2):228-238.http://www.ncbi.nlm.nih.gov/pubmed/27065588
Goyal M, Abrol P, Lal H: Parathyroid and calcium status in patients with thalassemia. Indian J Clin Biochem 2010, 25(4):385-387.http://www.ncbi.nlm.nih.gov/pubmed/21966110
Dresner Pollack R, Rachmilewitz E, Blumenfeld A, Idelson M, Goldfarb AW: Bone mineral metabolism in adults with beta-thalassaemia major and intermedia. Br J Haematol 2000, 111(3):902-907.http://www.ncbi.nlm.nih.gov/pubmed/11122154
Ferrara M, Matarese SM, Francese M, Borrelli B, Coppola A, Coppola L, Esposito L: Effect of VDR polymorphisms on growth and bone mineral density in homozygous beta thalassaemia. Br J Haematol 2002, 117(2):436-440.http://www.ncbi.nlm.nih.gov/pubmed/11972530
Pike JW: Genome-wide principles of gene regulation by the vitamin D receptor and its activating ligand. Mol Cell Endocrinol 2011, 347(1-2):3-10.http://www.ncbi.nlm.nih.gov/pubmed/21664239
Fang Y, van Meurs JB, d'Alesio A, Jhamai M, Zhao H, Rivadeneira F, Hofman A, van Leeuwen JP, Jehan F, Pols HA, Uitterlinden AG: Promoter and 3'-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: the rotterdam study. Am J Hum Genet 2005, 77(5):807-823.http://www.ncbi.nlm.nih.gov/pubmed/16252240
Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP: Genetics and biology of vitamin D receptor polymorphisms. Gene 2004, 338(2):143-156.http://www.ncbi.nlm.nih.gov/pubmed/15315818
Dimitriadou M, Christoforidis A, Fidani L, Economou M, Perifanis V, Tsatra I, Katzos G, Athanassiou-Metaxa M: Fok-I gene polymorphism of vitamin D receptor in patients with beta-thalassemia major and its effect on vitamin D status. Hematology 2011, 16(1):54-58.http://www.ncbi.nlm.nih.gov/pubmed/21269569
Smolders J, Damoiseaux J, Menheere P, Tervaert JW, Hupperts R: Fok-I vitamin D receptor gene polymorphism (rs10735810) and vitamin D metabolism in multiple sclerosis. J Neuroimmunol 2009, 207(1-2):117-121.http://www.ncbi.nlm.nih.gov/pubmed/19178954
Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, Haussler CA, Galligan MA, Thatcher ML, Encinas Dominguez C, Haussler MR: Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol 2001, 177(1-2):145-159.http://www.ncbi.nlm.nih.gov/pubmed/11377830
Deng HW, Shen H, Xu FH, Deng HY, Conway T, Zhang HT, Recker RR: Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density. J Bone Miner Res 2002, 17(4):678-686.http://www.ncbi.nlm.nih.gov/pubmed/11918225
Vupputuri MR, Goswami R, Gupta N, Ray D, Tandon N, Kumar N: Prevalence and functional significance of 25-hydroxyvitamin D deficiency and vitamin D receptor gene polymorphisms in Asian Indians. Am J Clin Nutr 2006, 83(6):1411-1419.http://www.ncbi.nlm.nih.gov/pubmed/16762954
Ethics Approval
Original ArticleHow to Cite
“BONE MINERAL DENSITY AND VITAMIN D RECEPTOR GENETIC VARIANTS IN EGYPTIAN CHILDREN WITH BETA THALASSEMIA ON VITAMIN D SUPPLEMENTATION” (2019) Mediterranean Journal of Hematology and Infectious Diseases, 11(1), p. e2019013. doi:10.4084/mjhid.2019.013.
