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

G. E. Elder, T. R J Lappin, A. B. Horne, V. F. Fairbanks, R. T. Jones, P. C. Winter, B. N. Green, James Hoyer, T. M. Reynolds, D. T B Shih, Daniel J Mc Cormick, K. S. Kubik, B. J. Madden, C. G. Head, D. Harvey, N. B. Roberts

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)321-328
Number of pages8
JournalMayo Clinic Proceedings
Volume73
Issue number4
StatePublished - 1998
Externally publishedYes

Fingerprint

Glycosylated Hemoglobin A
Codon
Diabetes Mellitus
Hemoglobins
Oxygen
Ion Exchange Chromatography
2,3-Diphosphoglycerate
Globins
Electrospray Ionization Mass Spectrometry
Protein Sequence Analysis
Isoelectric Focusing
Amino Acid Substitution
Molecular Structure
DNA Sequence Analysis
Electrophoresis
hemoglobin Old Dominion Burton-upon-Trent
Binding Sites
Polymerase Chain Reaction
Mutation
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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 journalArticle

Elder, GE, Lappin, TRJ, Horne, AB, Fairbanks, VF, Jones, RT, Winter, PC, Green, BN, Hoyer, J, Reynolds, TM, Shih, DTB, Mc Cormick, DJ, Kubik, KS, Madden, BJ, Head, CG, Harvey, D & Roberts, NB 1998, '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', Mayo Clinic Proceedings, vol. 73, no. 4, pp. 321-328.
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. / 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. In: Mayo Clinic Proceedings. 1998 ; Vol. 73, No. 4. pp. 321-328.
@article{cdc793fc235842fe89a58616f6c53c66,
title = "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",
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.",
author = "Elder, {G. E.} and Lappin, {T. R J} and Horne, {A. B.} and Fairbanks, {V. F.} and Jones, {R. T.} and Winter, {P. C.} and Green, {B. N.} and James Hoyer and Reynolds, {T. M.} and Shih, {D. T B} and {Mc Cormick}, {Daniel J} and Kubik, {K. S.} and Madden, {B. J.} and Head, {C. G.} and D. Harvey and Roberts, {N. B.}",
year = "1998",
language = "English (US)",
volume = "73",
pages = "321--328",
journal = "Mayo Clinic Proceedings",
issn = "0025-6196",
publisher = "Elsevier Science",
number = "4",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0031893354&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031893354&partnerID=8YFLogxK

M3 - Article

VL - 73

SP - 321

EP - 328

JO - Mayo Clinic Proceedings

JF - Mayo Clinic Proceedings

SN - 0025-6196

IS - 4

ER -