Severity differences in β-thalassaemia/haemoglobin E syndromes: implication of genetic factors

Summary. Genetic factors determining the difference in severity of anaemia in β-thalassaemia/HbE disease were studied in 90 patients who had haemoglobin levels, at steady state, ranging from 4.2 to 12.6 g/dl. Co-inheritance of α-thalassaemia 2 and haemoglobin Constant Spring could significantly decrease the severity of the disease. Inheritance of a β-thalassaemia chromosome with Xmn I cleavage site at position — 158 of the ^Gγ-globin gene which was linked to the haplotype - + - ++ or ++ - ++, was associated with a milder anaemia. Two copies of these alleles were necessary to produce a significant clinical effect. Increased expression of the ^Gγ-globin gene and higher production of haemoglobin F. which could reduce the overall globin chain imbalance, were also associated with homozygosity for the Xmn I cleavage site and thus with less severe anaemia. However, this effect was not seen in Xmn I site heterozygotes. Whether the effects of the Xmn I polymorphism, HbF concentration and ^Gγ/^Aγ ratio act separately or through common mechanisms in reducing anaemia remains to be ascertained.