Hb G-SAN JOSÈ VARIANT LEVELS CORRELATE WITH α-THALASSEMIA GENOTYPES

Abstract

Hb G-San Josè or β7(A4)Glu → Gly has been reported in Southern Italian or Mexican families. We have studied four families from Sicily and Campania, Southern Italy. In six carriers, the hemoglobin variant level ranged from 32 to 38%. In four double heterozygotes for Hb G-San Josè and α-thalassemia the variant level showed a strong correlation with the α-thalassemia genotype. In fact, the variant level was 15% when interacting with the −(α)^20.5/αα, 19.6% with the αα/α^{Poly A}α, and 24.8% with αα/α^{−5 nt}α genotypes. In two double heterozygotes for Hb G-San Josè and β⁺-IVS-I-6 (T → C) the hemoglobin variant level was 67%. These data show that the reduced synthesis of α chains causes drastic reduction of probability to form Hb G-San Josè in favor of the formation of Hb A. Moreover, this reduction, (i) correlates with the type of α-thalassemia genotype and with the degree of the α chain deficiency, and (ii) is, most probably, more marked than the degree of α chain reduction. The minor affinity of the β chain variant for the α chains associated with the reduced synthesis of the α chains is probably the principal cause of the variant hemoglobin reduction. Moreover, the rapid removal of the abnormal chains by proteolytic enzymes must have an essential role in order to reduce the chain variant pool. These conclusions are in agreement with the results obtained in reticulocyte and in vitro recombination experiments.