The Effect of α-Thalassemia on the Level of Hybrid Hemoglobin Variants in Heterozygotes

Abstract

The influence of a relative deficiency in α chain production on the amount of Hemoglobins Kenya, P-Nilotic, and Lepore was determined. The level of these hybrid hemoglobins in heterozygotes was correlated to various states of α chain deficiency by: 1) quantitation of the variants in blood samples and comparing these data with the number of α globin genes determined by gene mapping, 2) in vitro recombination experiments involving isolated non-α chains and normal α chains, and 3) in vitro heat stability analyses of the isolated hemoglobins. Hb Kenya, composed of normal α and γ-β hybrid chains, is heat labile, has a decreased ability to combine with α chains, and its level in heterozygotes is greatly decreased when a concomitant α-chain deficiency (α-thalassemia) is present. Such a posttranslational control mechanism was not observed for Hb Lepore, with normal α chains and δ-β hybrid chains, and Hb P-Nilotic, with normal α chains and β-δ hybrid chains. The latter two variants are heat stable, and their hybrid chains combine equally well as normal β chains with normal α chains. Hb P-Nilotic is more heat stable than Hb A and its in vitro formation is increased over that of Hb S, and perhaps even Hb A, in conditions of severe α chain deficiency.