Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Hemmat Expressway, IBTO Building, Tehran, 1449613111, Iran.
Department of Hemovigilance, Iranian Blood Transfusion Organization, Tehran, Iran.
BMC Med Genet. 2020 Apr 8;21(1):75. doi: 10.1186/s12881-020-01011-3.
β Thalassemia is one of the most common groups of hereditary haemoglobinopathies. Affected people with thalassemia major are dependent on regular blood transfusion which on the long term leads to iron overload. Hepcidin is a peptide hormone and an important regulator of iron homeostasis, especially in thalassemia. Expression of this hormone is influenced by polymorphisms within the hepcidin gene, HAMP. Several studies emphasized the role of single nucleotide polymorphisms (SNPs) located in the promoter region of the gene. This study aimed to analyze the association between three SNPs in promoter of HAMP, c.-582A > G, c.-443C > T, and c.-153C > T, with iron overload in β-thalassemia major patients.
A total of 102 samples from β thalassemia major patients were collected. Genomic DNA was extracted and segments of DNA encompassing rs10421768 and rs142126068 were sequenced. Statistical analysis was performed by SPSS Statistics 23 using independent t test and Fisher's exact test.
A total of 102 adult β-thalassemia major patients were genotyped for three SNPs in the promoter region of HAMP gene by PCR and direct sequencing. Most of the patients (71.3%) were iron overloaded (based on plasma ferritin > 1000 ng/ml) in spite of receiving regular iron-chelating therapy. Our analysis revealed a statistically significant difference between the level of cardiac iron accumulation and c.-582A > G variant (p = 0.02). For c.-443C > T statistical analysis was on the edge of the significant relationship between the minor allele and serum ferritin (p = 0.058). All samples were homozygous for allele C of c.-153C > T.
Despite chelating therapy, iron overload is still one of the main complications of thalassemia. Our findings and others emphasize the role of hepcidin -582A > G polymorphism as a key component of iron homeostasis in these patients.
β 地中海贫血是最常见的遗传性血红蛋白病之一。患有重型地中海贫血的患者依赖于定期输血，长期输血会导致铁过载。铁调素是一种肽激素，是铁稳态的重要调节剂，特别是在地中海贫血中。这种激素的表达受铁调素基因 HAMP 内多态性的影响。几项研究强调了位于基因启动子区域的单核苷酸多态性 (SNP) 的作用。本研究旨在分析 HAMP 基因启动子中的三个 SNP（c.-582A>G、c.-443C>T 和 c.-153C>T）与重型 β 地中海贫血患者铁过载之间的关系。
共采集 102 例重型 β 地中海贫血患者样本。提取基因组 DNA，对 rs10421768 和 rs142126068 片段进行测序。采用 SPSS Statistics 23 软件进行独立 t 检验和 Fisher 确切检验进行统计分析。
采用 PCR 直接测序法对 HAMP 基因启动子区的三个 SNP 对 102 例成年重型 β 地中海贫血患者进行基因分型。尽管接受了定期的铁螯合治疗，但大多数患者（71.3%）存在铁过载（根据血浆铁蛋白>1000ng/ml）。我们的分析显示，心脏铁蓄积水平与 c.-582A>G 变异体之间存在统计学差异（p=0.02）。对于 c.-443C>T，次要等位基因与血清铁蛋白之间存在统计学意义上的关系（p=0.058）。所有样本均为 c.-153C>T 的等位基因 C 纯合子。
尽管进行了螯合治疗，铁过载仍然是地中海贫血的主要并发症之一。我们的研究结果和其他研究结果强调了铁调素-582A>G 多态性作为这些患者铁稳态关键组成部分的作用。
