A New α Chain Variant HB Tonosho [α110(G17)ALA→THR]: Subunit Dissociation During Cation Exchange Chromatography for HB A_1c Assay

Abstract

A new α chain variant, α110(G17)Ala→Thr, was detected because of subunit dissociation during the determination of the Hb A_1c by automated cation exchange high performance liquid chromatography. The abnormal hemoglobin overlapped the cathodic edge of the band of Hb A in isoelectrofocusing. It was slightly unstable in the isopropanol test and had a slightly increased oxygen affinity. The abnormal α chain eluted slightly faster than the normal α chain in reversed phase high performance liquid chromatography. The amino acid substitution was determined by purification of S-alkylated αT-12, 13 tryptic peptide, chymotryptic digestion, and sequencing of an octapeptide α110-117. The abnormal α chain comprised about 14% of the total α chain. A biosynthetic study did not suggest selective loss of the abnormal chain in reticulocytes.