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Hadeer A Abbassy
Reham Abdel Haleem Abo Elwafa
Omneya Magdy Omar


Vitamin D, VDR genetic variants, BMD, Osteoporosis, DEXA, Thalassemia.


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.


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1. Higgs DR, Engel JD, Stamatoyannopoulos G: Thalassaemia. Lancet 2012, 379(9813):373-383.

2. 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.

3. Kesse-Adu R, Howard J: Inherited anaemias: sickle cell and thalassaemia. Medicine, 41(4):219-224.

4. 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.

5. Borgna-Pignatti C, Gamberini MR: Complications of thalassemia major and their treatment. Expert Rev Hematol 2011, 4(3):353-366.

6. 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.

7. Sunyecz JA: The use of calcium and vitamin D in the management of osteoporosis. Ther Clin Risk Manag 2008, 4(4):827-836.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. Bikle DD: Vitamin D and bone. Curr Osteoporos Rep 2012, 10(2):151-159.

17. Soliman A, De Sanctis V, Yassin M: Vitamin d status in thalassemia major: an update. Mediterr J Hematol Infect Dis 2013, 5(1):e2013057.

18. 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.

19. 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.

20. 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.

21. Goyal M, Abrol P, Lal H: Parathyroid and calcium status in patients with thalassemia. Indian J Clin Biochem 2010, 25(4):385-387.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.