TY - JOUR
T1 - 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
T2 - Structure, Function, and DNA Sequence
AU - Elizabeth Elder, G.
AU - Lappin, Terry R.J.
AU - Hörne, Allen B.
AU - Fairbanks, Virgil F.
AU - Jones, Richard T.
AU - Winter, Paul C.
AU - Green, Brian N.
AU - Hoyer, James D.
AU - Reynolds, Timothy M.
AU - Shih, Daniel T.B.
AU - Mccormick, Daniel J.
AU - Kubik, Kathleen S.
AU - Madden, Benjamin J.
AU - Head, Charlotte G.
AU - Harvey, D.
AU - Roberts, Norman B.
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 1998
Y1 - 1998
N2 - Objective: 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. Results: 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. Conclusion: 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 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.
AB - Objective: 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. Results: 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. Conclusion: 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 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.
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U2 - 10.1016/s0025-6196(11)63697-5
DO - 10.1016/s0025-6196(11)63697-5
M3 - Article
C2 - 9559035
AN - SCOPUS:0031893354
SN - 0025-6196
VL - 73
SP - 321
EP - 328
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 4
ER -