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Shaimaa Sahmoud
Mostafa S. Ibrahim
Eman A. Toraih
Noha Kamel
Manal Fawzy
Samar Elfiky


Bone mineral density; Gene expression; Genotyping; Real-Time PCR; RXRA; Single nucleotide polymorphism; Thalassemia; VDBP; VDR


Introduction: The reduced rate of bone formation despite the availability of vitamin D has been reported in ?-thalassemia.  This suggests genetic factors together with environmental one can 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 ?-thalassemia children in correlation with bone mineral density (BMD).

Patients and methods: Forty-four ?-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 ?-thalassemia children compared to controls (P = 0.001 and <0.001, respectively) and showed higher values in ?-thalassemia major relative to ?-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: ?-Thalassemia children had higher expression levels of PBMN VDR/RXRA. VDBP rs4701 variant was associated with osteoporosis in our ?-thalassemia patients on vitamin D supplementation. Further large-scale studies in other ethnic populations are warranted.


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