Al-Allawi Nasir A S, Puehringer Helene, Raheem Ruzaiqah A, Oberkanins Christian
1 Faculty of Medical Sciences, Scientific Research Center, University of Duhok , Duhok, Iraq .
Genet Test Mol Biomarkers. 2015 May;19(5):242-7. doi: 10.1089/gtmb.2014.0310. Epub 2015 Mar 9.
To determine the molecular basis of β-thalassemia intermedia (TI) and the contribution of the three hemoglobin F (HbF) quantitative trait loci (QTLs) on chromosomes 11, 2, and 6 to the milder phenotype, a total of 102 Iraqi Arab patients with TI were studied. The β and α genotypes as well as HBG2 g. 158 C>T (rs7482144), BCL11A (rs1427407 and rs10189857), and HBS1L-MYB (rs28384513 and rs9399137) by multiplex polymerase chain reaction and reverse hybridization were studied. A total of 21 different β-thalassemia mutations arranged in 35 different genotypes were identified. The genotypes encompassed β(+)/β(+) mutations in 33 cases, β(+)/β(0) in 17 cases, β(0)/β(0) in 47 cases, β(0)/wild type in 3 and β(0)/Hb E in 2 cases. The most common was IVS-II-1 (G>A)/IVS-II-1 (G>A), followed by IVS-I-6 (T>C)/IVS-I-6 (T>C) and IVS-I-110 (G>A)/IVS-I-110 (G>A), in 31.4%, 17.6%, and 6.9%, respectively. Alpha-thalassemia mutations were found in 15.2% of those homozygous for the β-mutations, while α gene triplication was identified in all three heterozygotes. Of the five QTLs tested, only rs7482144 and rs10189857 were significantly associated with β(0)/β(0) when compared to β(+)/β(+), with odds ratios of 6.4 (95% confidence interval [CI] 2.9-14.0) and 3.2 (95% CI 1.2-8.6), respectively. In conclusion, this study has demonstrated that among Iraqi patients with thal intermedia, the main contributors to the milder phenotype were β(+) alleles, XmnI polymorphism, and BCL11A (rs10189857), while other QTLs on chromosomes 2 and 6, as well as alpha-thalassemia, were not significantly relevant.
为了确定中间型β地中海贫血（TI）的分子基础以及11号、2号和6号染色体上的三个血红蛋白F（HbF）数量性状基因座（QTL）对较轻表型的贡献，我们对102例伊拉克阿拉伯TI患者进行了研究。通过多重聚合酶链反应和反向杂交研究了β和α基因型以及HBG2 g.158 C>T（rs7482144）、BCL11A（rs1427407和rs10189857）和HBS1L-MYB（rs28384513和rs9399137）。共鉴定出21种不同的β地中海贫血突变，分布在35种不同的基因型中。这些基因型包括33例β(+)/β(+)突变、17例β(+)/β(0)、47例β(0)/β(0)、3例β(0)/野生型和2例β(0)/Hb E。最常见的是IVS-II-1（G>A）/IVS-II-1（G>A），其次是IVS-I-6（T>C）/IVS-I-6（T>C）和IVS-I-110（G>A）/IVS-I-110（G>A），分别占31.4%、17.6%和6.9%。在β突变纯合子中，15.2%发现了α地中海贫血突变，而在所有三个杂合子中均鉴定出α基因三倍体。在测试的五个QTL中，与β(+)/β(+)相比，只有rs7482144和rs10189857与β(0)/β(0)显著相关，优势比分别为6.4（95%置信区间[CI]2.9 - 14.0）和3.2（95%CI 1.2 - 8.6）。总之，本研究表明，在伊拉克中间型地中海贫血患者中，较轻表型的主要贡献因素是β(+)等位基因、XmnI多态性和BCL11A（rs10189857），而2号和6号染色体上的其他QTL以及α地中海贫血则无显著相关性。
