Miri-Moghaddam Ebrahim, Bahrami Sara, Naderi Majid, Bazi Ali, Karimipoor Morteza
Associate Professor, Genetics of Non-Communicable Disease Research Center, zahedan University of Medical Sciences, zahedan, Iran.
CardioVascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Int J Hematol Oncol Stem Cell Res. 2017 Apr 1;11(2):165-171.
Xmn-1 polymorphism of 𝜸globin gene (HBG2) is a prominent quantitative trait loci (QTL) in β-thalassemia intermediate (β-TI). In current study, we evaluated the frequency of Xmn-1 polymorphism and its association with β-globin gene (HBB) alleles and Hb F level in β-TI patients in Sistan and Balouchestan province, south-east of Iran. 45 β-TI patients were enrolled. HBB gene mutations and Xmn-1 polymorphism were determined by amplification-refractory mutation system (ARMS) PCR method. Hemoglobin profile was determined using capillary electrophoresis. The study participants consisted of 26 (58%) males and 19 (42%) females. Mean age of the patients was 10.7±3.1 years old. Overall, Xmn-1 polymorphism was observed in 28 (62%) patients. Homozygous (TT) and heterozygous (CT) genotypes of the polymorphism represented with frequencies of 12 (26%) and 16 (35%), respectively. Main recognized HBB gene mutation was IVSI-5(G>C) with homozygous frequency of 44%. Non-zero (β) alleles of HBB gene constituted 11.1 % (4 patients with heterozygous β and one with homozygous β genotype). Hb F level was significantly higher in patients with at least one Xmn-1allele (67.9±[Formula: see text]17.9%) than those without the polymorphism (19.5±20.3%, P<0.0001). Also, patients with homozygous genotype demonstrated significantly higher Hb F compared to heterozygous (CT) cases (respective percentages of 85±[Formula: see text]6.8 and 54.7±[Formula: see text]10.5, p<0.0001). Our results highlighted the role of Xmn-1 polymorphism as the main phenotypic modifier in β-TI patients in Sistan and Balouchestan province.
γ珠蛋白基因（HBG2）的Xmn-1多态性是β地中海贫血中间型（β-TI）中一个显著的数量性状位点（QTL）。在本研究中，我们评估了伊朗东南部锡斯坦-俾路支斯坦省β-TI患者中Xmn-1多态性的频率及其与β珠蛋白基因（HBB）等位基因和Hb F水平的关联。纳入了45例β-TI患者。采用扩增阻滞突变系统（ARMS）PCR法检测HBB基因突变和Xmn-1多态性。使用毛细管电泳测定血红蛋白谱。研究参与者包括26名（58%）男性和19名（42%）女性。患者的平均年龄为10.7±3.1岁。总体而言，28例（62%）患者观察到Xmn-1多态性。该多态性的纯合子（TT）和杂合子（CT）基因型频率分别为12例（26%）和16例（35%）。主要识别的HBB基因突变是IVSI-5（G>C），纯合子频率为44%。HBB基因的非零（β）等位基因占11.1%（4例杂合子β患者和1例纯合子β基因型患者）。至少有一个Xmn-1等位基因的患者Hb F水平（67.9±[公式：见原文]17.9%）显著高于无该多态性的患者（19.5±20.3%，P<0.0001）。此外，纯合子基因型患者的Hb F水平显著高于杂合子（CT）患者（分别为85±[公式：见原文]6.8和54.7±[公式：见原文]10.5，p<0.0001）。我们的结果突出了Xmn-1多态性作为锡斯坦-俾路支斯坦省β-TI患者主要表型修饰因子的作用。
