Hemoglobin Old Dominion/Burton-upon-Trent, β143 (H21) His→Tyr, Codon 143 CAC→TAC—a Variant With Altered Oxygen Affinity That Compromises Measurement of Glycated Hemoglobin in Diabetes Mellitus: Structure, Function, and DNA Sequence

• Published in: Mayo Clinic proceedings Vol. 73; no. 4; pp. 321 - 328
• Main Authors: Elder, G. Elizabeth, Lappin, Terry R.J., Horne, Allen B., Fairbanks, Virgil F., Jones, Richard T., Winter, Paul C., Green, Brian N., Hoyer, James D., Reynolds, Timothy M., Shih, Daniel T.-B., McCormick, Daniel J., Kubik, Kathleen S., Madden, Benjamin J., Head, Charlotte G., Harvey, D., Roberts, Norman B.
• Format: Journal Article
• Language: English
• Published: Rochester, MN Elsevier Inc 01.04.1998; Mayo Medical Ventures
• Subjects: Biological and medical sciences; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Medical sciences; ESI-MS; m/z; DPG; P50; HB A lc; HPLC; Endocrinopathy; Human; Diabetes mellitus; Exploration; Ion exchange chromatography; Irish; Case study; Polymerase chain reaction; Gene; Hemoglobin A1c; DNA; Mutation; Molecular biology
• ISSN: 0025-6196; 1942-5546
• DOI: 10.1016/S0025-6196(11)63697-5

To determine the nature and characteristics of a unique hemoglobin variant that causes a spurious increase in glycated hemoglobin (Hb Alc). Blood specimens from four unrelated persons with this hemoglobin variant were examined by conventional laboratory methods, including electrophoresis, high-performance ion-exchange chromatography, and isoelectric focusing; by amino acid sequence analysis, polymerase chain reaction-based DNA sequence analysis, and electrospray ionization mass spectrometry, to establish the molecular structure; and by studies of oxygen affinity under varied conditions, to define the functional characteristics of the hemoglobin variant. The unique hemoglobin variant observed in these four cases is due to the mutation CAC→TAC, at β- globin gene codon 143, corresponding to β143 (H21) His→Tyr. This amino acid substitution affects an important 2,3-diphosphoglycerate binding site and slightly increases the oxygen affinity of the hemoglobin variant. A hitherto unrecognized hemoglobin variant, encountered in four unrelated persons of Irish or Scots-Irish ancestry, hemoglobin Old Dominion/Burtonupon-Trent, β143 (H21) His→Tyr, has now been characterized at the molecular, structural, and functional levels. Although it is associated with a slight increase in oxygen affinity, it is without hematologic effect, and its only clinical significance is that it coelutes with Hb Alc on ionexchange chromatography and thereby causes a spurious increase in Hb Alc and compromises the use of this analyte to monitor the treatment of diabetes mellitus.