Is the trimodality of Hb Leslie (α2β2131Gln→ 0) in heterozygotes the result of a variable number of active α‐chain genes? Evidence for posttranslational control of hemoglobin synthesis

Abstract

Whether the trimodality in the relative concentration of the hemoglobin variant Hb Leslie in heterozygotes (Huisman, Hemoglobin 1: 349–382, 1977) is due to a polymorphism of the α‐chain structural genes was investigated by conventional incubation of reticulocytes with 14C‐leucine. In addition, an aliquot from each of the incubations was incubated under the same conditions but without isotope. Three Hb Leslie heterozygotes with presumably four, three (heterozygous α‐thalassemia‐2), and two (homozygous α‐thalassemia‐2) active α‐chain genes and with 33%, 22%, and 11% Hb Leslie respectively, and one patient with the Hb Leslie β0‐thalassemia condition with more than 85% Hb Leslie were studied. The data indicate that βLeslie chains have a lower affinity for α chains than βA chains. A concomitant α‐chain deficiency results in a reduced incorporation of βLeslie chains into the tetrameric Hb Leslie molecules, while the quantity of Hb Leslie produced correlates with the degree of α‐chain deficiency. Excess of βLeslie chains is preferentially degraded.