Abstract
Objective: To determine the nature and characteristics of a unique hemoglobin variant that causes a spurious increase in glycated hemoglobin (Hb A(1c). 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/Burton- upon-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 A(1c) on ion- exchange chromatography and thereby causes a spurious increase in Hb A(1c) and compromises the use of this analyte to monitor the treatment of diabetes mellitus.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 321-328 |
| Number of pages | 8 |
| Journal | Mayo Clinic Proceedings |
| Volume | 73 |
| Issue number | 4 |
| State | Published - 1998 |
| Externally published | Yes |
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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. / Elder, G. E.; Lappin, T. R J; Horne, A. B.; Fairbanks, V. F.; Jones, R. T.; Winter, P. C.; Green, B. N.; Hoyer, James; Reynolds, T. M.; Shih, D. T B; Mc Cormick, Daniel J; Kubik, K. S.; Madden, B. J.; Head, C. G.; Harvey, D.; Roberts, N. B.
In: Mayo Clinic Proceedings, Vol. 73, No. 4, 1998, p. 321-328.Research output: Contribution to journal › Article
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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 - Elder, G. E.
AU - Lappin, T. R J
AU - Horne, A. B.
AU - Fairbanks, V. F.
AU - Jones, R. T.
AU - Winter, P. C.
AU - Green, B. N.
AU - Hoyer, James
AU - Reynolds, T. M.
AU - Shih, D. T B
AU - Mc Cormick, Daniel J
AU - Kubik, K. S.
AU - Madden, B. J.
AU - Head, C. G.
AU - Harvey, D.
AU - Roberts, N. B.
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 A(1c). 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/Burton- upon-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 A(1c) on ion- exchange chromatography and thereby causes a spurious increase in Hb A(1c) 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 A(1c). 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/Burton- upon-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 A(1c) on ion- exchange chromatography and thereby causes a spurious increase in Hb A(1c) and compromises the use of this analyte to monitor the treatment of diabetes mellitus.
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M3 - Article
VL - 73
SP - 321
EP - 328
JO - Mayo Clinic Proceedings
JF - Mayo Clinic Proceedings
SN - 0025-6196
IS - 4
ER -