α-Haemoglobin stabilising protein is a quantitative trait gene that modifies the phenotype of β-thalassaemia
α-Haemoglobin stabilising protein is a quantitative trait gene that modifies the phenotype of β-thalassaemia
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DOI：
10.1111/j.1365-2141.2006.06075.x
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发表时间：
2006-06-01
影响因子：
6.5
通讯作者：
Thein, Swee L.
中科院分区：
文献类型：
--
作者：
Lai, Mei I.;Jiang, Jie;Thein, Swee L.
有研究表明，α -血红蛋白稳定蛋白（AHSP）的水平或功能的改变可能解释了β -地中海贫血的一些临床变异。α -血红蛋白稳定蛋白是一种与游离α -（血红）球蛋白特异性结合的红细胞特异性蛋白。为了评估AHSP表达的变化，我们采用定量逆转录-聚合酶链反应测定了103名健康人循环网状细胞的mRNA水平。AHSP表达变化高达三倍，与年龄或性别无关。对AHSP位点的系统调查确定了8个序列变异，其中6个是常见的。四种常见的变异，包括在假定的启动子中的较长的均聚物（T18），与AHSP的表达密切相关。在K562细胞中进行的报告基因实验显示，较短的（T15）报告基因的活性相对低于T18报告基因。在一项对9名患有-地中海贫血和三倍α -珠蛋白基因（α α α / α α）杂合的贫血患者的研究中，短均聚物的频率高于预期。AHSP的表达是可变的，cis控制占其方差的一部分。在一些家庭中，与AHSP基因型相关的AHSP水平的细微改变似乎是血液学表型的相关促成因素。
It has been suggested that altered levels or function of alpha-haemoglobin stabilising protein (AHSP), an erythroid-specific protein that binds specifically to free alpha-(haemo)globin, might account for some of the clinical variability in beta-thalassaemia. To assess the variation of AHSP expression, mRNA levels in circulating reticulocytes of 103 healthy individuals were measured by quantitative reverse transcription-polymerase chain reaction. AHSP expression varied up to threefold, and did not correlate with age or sex. A systematic survey of the AHSP locus identified eight sequence variants, of which six were common. Four common variants, including the longer homopolymer (T18) in the putative promoter, are strongly associated with AHSP expression. Reporter assays in K562 cells showed that the activity of the shorter (T15) reporter was relatively lower than that of the T18 reporter. In a study of nine anaemic patients who were heterozygous for beta-thalassaemia and also heterozygous for the triplicated alpha-globin gene (alpha alpha alpha/alpha alpha), frequency of the shorter homopolymer was higher than expected. AHSP expression is variable, with cis control accounting for some of its variance. In some families, the subtle altered levels in AHSP related to the AHSP genotype appears to be a relevant contributory factor in the haematological phenotype.