SEVERITY DIFFERENCES IN BETA-THALASSEMIA HEMOGLOBIN-E SYNDROMES - IMPLICATION OF GENETIC-FACTORS

Genetic factors determining the difference in severity of anaemia in beta-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 alpha-thalassaemia 2 and haemoglobin Constant Spring could significantly decrease the severity of the disease. Inheritance of a beta-thalassaemia chromosome with Xmn I cleavage site at position - 1 5 8 of the (G)gamma-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 (G)gamma-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 (G)gamma/(A)gamma ratio act separately or through common mechanisms in reducing anaemia remains to be ascertained.