Sahmoud Shaimaa, Ibrahim Mostafa S, Toraih Eman A, Kamel Noha, Fawzy Manal S, Elfiky Samar
Pediatric Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Diagnostic Radiology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Mediterr J Hematol Infect Dis. 2020 Jul 1;12(1):e2020037. doi: 10.4084/MJHID.2020.037. eCollection 2020.
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 / expression signature, and two variants in a pilot sample of Egyptian β-thalassemia children in correlation with bone mineral density (BMD).
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) / expression levels were quantified by Real-Time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). 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).
/ expressions were significantly higher in β-thalassemia children compared to controls ( = 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, rs4701 genotyping revealed lower BMD-L4 and a higher frequency of osteoporosis.
β-Thalassemia children had higher expression levels of PBMN /. 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.
据报道，β地中海贫血患者尽管有维生素D供应，但骨形成率仍降低。遗传因素与环境因素可能与这种情况有关。由于维生素D结合蛋白（VDBP）维持维生素D的生物利用度，维生素D与维生素D受体（VDR）-视黄酸X受体α（RXRA）异二聚体结合以发挥其分子作用，我们推测维生素D代谢轴表达特征和变体可能是地中海贫血中骨转换/疾病的潜在分子候选因素。为此，本研究旨在分析埃及β地中海贫血儿童试点样本中的/表达特征以及两个变体与骨矿物质密度（BMD）的相关性。
招募了44名螯合良好的β地中海贫血儿童和40名无关对照。测量血清骨化学指标。通过实时定量逆转录聚合酶链反应（qRT-PCR）定量外周血单个核细胞（PBMN）/表达水平。通过实时等位基因鉴别分析鉴定rs7041和rs4588变体。所有患者均接受腰椎双能X线吸收法（DEXA）检查。
与对照组相比，β地中海贫血儿童的/表达明显更高（分别为=0.001和<0.001），并且重型β地中海贫血相对于中间型β地中海贫血显示出更高的值。两个基因的表达水平与性别或BMD均无关。然而，rs4701基因分型显示较低的BMD-L4和较高的骨质疏松症发生率。
β地中海贫血儿童的PBMN /表达水平较高。在我们接受维生素D补充的β地中海贫血患者中，rs4701变体与骨质疏松症有关。有必要在其他种族人群中进行进一步的大规模研究。
