Traeger J, Wood W G, Clegg J B, Weatherall D J
Nature. 1980 Dec 4;288(5790):497-9. doi: 10.1038/288497a0.
Haemoglobin E (alpha 2 beta 2(26)Glu leads to Lys) is one of the commonest haemoglobin variants. There are an estimated 30 million carriers of the beta E gene in South-East Asia, where they comprise more than 50% of the population in some areas; however, the reasons for this high frequency have never been adequately explained. Homozygotes for HbE may be midly anaemic, but they do not have any clinical disability. However, individuals heterozygous for both beta E and beta thalassaemia (HbE/beta thalassaemia) have a severe clinical disorder which in some cases may approach that seen in homozygous beta thalassaemia 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 beta thalassaemia to produce 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 beta E chain is inefficiently synthesized and produces the phenotype of a mild form of beta thalassaemia; hence, when inherited together with beta thalassaemia it causes a marked beta-chain deficit. Furthermore, the mechanism for the defective production of beta E chains seems to be a reduction of beta E 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 beta globin gene.
血红蛋白E（α2β2(26)谷氨酸突变为赖氨酸）是最常见的血红蛋白变异体之一。据估计，东南亚有3000万βE基因携带者，在某些地区，他们占当地人口的50%以上；然而，这种高频率出现的原因从未得到充分解释。HbE纯合子可能有轻度贫血，但没有任何临床残疾。然而，βE和β地中海贫血的杂合子个体（HbE/β地中海贫血）患有严重的临床疾病，在某些情况下，其严重程度可能接近纯合子β地中海贫血，并且这是印度次大陆和东南亚有症状地中海贫血最常见的形式。血红蛋白E是唯一一种与β地中海贫血相互作用导致严重疾病的常见结构变异体，其相互作用的潜在机制尚不清楚。我们研究了几个HbE纯合子和杂合子，并在此表明βE链合成效率低下，产生了轻度β地中海贫血的表型；因此，当与β地中海贫血一起遗传时，它会导致明显的β链缺陷。此外，βE链产生缺陷的机制似乎是βE mRNA减少，这在由单个氨基酸取代（可能是β珠蛋白基因DNA中的单个核苷酸变化）引起的疾病中是一个最意想不到的发现。
