Hb E and α-Thalassemia; Variability in the Assembly of β^E Chain Containing Tetramers

Abstract

The level of Hb E (including Hb A₂) was quantitated in 30 adult Hb E heterozygotes by cation exchange high performance liquid chromatography; in 20 subjects the a-globin gene status was determined by gene mapping and polymerase chain reaction methodology. A decrease in Hb E level was observed which was directly related to the type of a-thalassemia that was present; the lowest percentage of Hb E (and Hb A₂) was 10.2%, seen in two persons with Hb Constant Spring (CS)-Hb H disease (α^CSα/−). Similar analyses were made for several newborn babies with a Hb E heterozygosity; the Hb E level was determined as β^E by a reversed phase high performance liquid chromatographic procedure. One baby with Hb E trait and Hb H disease (-α/−) had a β^E level of 17.7% (as % of β^A + β^E) comparable to that seen for adults with an identical genotype. One fetus with hydrops fetalis (−/−) and Hb E trait had low β^E and β^A levels which, however, were nearly identical (1.5 and 1.3% of the total hemoglobin). These β chains apparently combine with the embryonic ζ chain to form Hb Portland-ll (ζ₂β₂^A) and a variant of this hemoglobin (ζ₂β₂^E). The affinity of the two β chains for the ζ chain must be the same and quite different from that for the α chain. Moreover, this single observation suggests an equal synthesis of β^A and β^E chains, the low level of Hb E in adult heterozygotes being primarily the result of a greatly decreased rate of assembly of αβ^E dimers.