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

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To determine the nature and characteristics of a unique hemoglobin variant that causes a spurious increase in glycated hemoglobin (Hb A1c).

Material and Methods

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[right arrow]TAC, at beta-globin gene codon 143, corresponding to beta 143 (H21) His[right arrow]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/Burton-upon-Trent, beta 143 (H21) His[right arrow]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 A1c on ion-exchange chromatography and thereby causes a spurious increase in Hb A1c and compromises the use of this analyte to monitor the treatment of diabetes mellitus.

Mayo Clin Proc 1998;73


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