Defective synthesis of HbE is due to reduced levels of βE mRNA
Defective synthesis of HbE is due to reduced levels of βE mRNA
复制标题
HbE 合成缺陷是由于 βE mRNA 水平降低所致
作者：
J. Traeger;W. Wood;J. Clegg;D. Weatherall;P. Wasi
血红蛋白E(α2β226Glu→Lys)是最常见的血红蛋白变异体之一。据估计，东南亚有3,000万βE基因携带者，它们占某些地区人口的50%以上1，2；然而，这种高频率的原因从未得到充分解释。HBe纯合子可能有轻度贫血，但他们没有任何临床残疾3，4。然而，βE和β地中海贫血症(HBe/β地中海贫血症)杂合子个体有严重的临床疾病，在某些情况下可能接近纯合子β地中海贫血症3，5，6，这是迄今为止印度次大陆和东南亚最常见的症状性地中海贫血症形式。血红蛋白E是唯一一种常见的结构变异，它与β地中海贫血症相互作用而产生如此严重的疾病，其潜在机制尚不清楚。我们已经研究了几种HBe纯合子和杂合子，这里显示βE链合成效率低下，并产生轻度β地中海贫血症的表型；因此，当与β地中海贫血症一起遗传时，它会导致显著的β链缺陷。此外，βE链缺陷产生的机制似乎是βE基因的减少，这在由单个氨基酸替代引起的疾病中是最出人意料的发现，可能是由于β珠蛋白基因的DNA单核苷酸变化引起的。
Haemoglobin E (α2β226GlU→Lys) is one of the commonest haemoglobin variants. There are an estimated 30 million carriers of the βE gene in South-East Asia, where they comprise more than 50% of the population in some areas1,2; however, the reasons for this high frequency have never been adequately explained. Homozygotes for HbE may be mildly anaemic, but they do not have any clinical disability3,4. However, individuals heterozygous for both βE and β thalassaemia (HbE/β thalassaemia) have a severe clinical disorder which in some cases may approach that seen in homozygous β thalassaemia3,5,6 and which is by far the commonest form of symptomatic thalassaemia in the Indian subcontinent and South-East Asia. Haemoglobin E is the only common structural variant which interacts with β thalassaemia to produce such a severe disorder and the underlying mechanism of the interaction is not known. We have studied several homozygotes and heterozygotes for HbE and show here that the βE chain is inefficiently synthesized and produces the phenotype of a mild form of β thalassaemia; hence, when inherited together with β thalassaemia it causes a marked β-chain deficit. Furthermore, the mechanism for the defective production of βE chains seems to be a reduction of βE mRNA, a most unexpected finding in a disorder caused by a single amino acid substitution and presumably by a single nucleotide change in the DNA of the β globin gene.