Garner Chad, Dew Tracy K, Sherwood Roy, Rees David, Thein Swee Lay
Department of Environmental Analysis and Design, Division of Epidemiology, University of California, Irvine, CA, USA.
Br J Haematol. 2003 Oct;123(2):353-8. doi: 10.1046/j.1365-2141.2003.04600.x.
To assess and define the effects of heterocellular hereditary persistence of fetal haemoglobin (HPFH) on the haematological phenotype of heterozygous beta-thalassaemia, we have studied a large kindred that included a total of 204 subjects with 60 beta-thalassaemia carriers, of whom 35 were also heterozygous, and five homozygous, for heterocellular HPFH. The study was possible because of the homogeneity of the beta-thalassaemia mutation and the ability to genotype the heterocellular HPFH allele. Heterocellular HPFH had a significant effect on the mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and haemoglobin (Hb) A2 values in the beta-thalassaemia carriers and accounted for 29%, 30% and 24% of their respective variances. beta-thalassaemia subjects with heterocellular HPFH had higher MCV and MCH values, concomitant with lower levels of Hb A2, and a reduced ineffective erythropoiesis. We conclude that co-inheritance of heterocellular HPFH leads to a primary increase in gamma-chain synthesis in beta-thalassaemia trait and can be another confounding factor in the use of red cell indices and Hb A2 levels in population screening for beta-thalassaemia.
为了评估和确定胎儿血红蛋白异细胞遗传性持续存在（HPFH）对杂合子β地中海贫血血液学表型的影响，我们研究了一个大家族，其中共有204名受试者，包括60名β地中海贫血携带者，其中35名同时为杂合子，5名是纯合子的异细胞HPFH患者。由于β地中海贫血突变的同质性以及对异细胞HPFH等位基因进行基因分型的能力，该研究得以进行。异细胞HPFH对β地中海贫血携带者的平均红细胞血红蛋白含量（MCH）、平均红细胞体积（MCV）和血红蛋白（Hb）A2值有显著影响，分别占其各自方差的29%、30%和24%。患有异细胞HPFH的β地中海贫血受试者具有较高的MCV和MCH值，同时Hb A2水平较低，无效红细胞生成减少。我们得出结论，异细胞HPFH的共同遗传导致β地中海贫血特征中γ链合成的原发性增加，并且可能是在人群中筛查β地中海贫血时使用红细胞指数和Hb A2水平的另一个混杂因素。
