Hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (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 (HbA1c).

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 beta-globin gene codon 143, corresponding to beta 143 (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, beta 143 (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 HbA1c on ion-exchange chromatography and thereby causes a spurious increase in HbA1c and compromises the use of this analyte to monitor the treatment of diabetes mellitus.

• Authors: G E Elder, T R Lappin, A B Horne, V F Fairbanks, R T Jones, P C Winter, B N Green, J D Hoyer, T M Reynolds, D T Shih, D J McCormick, K S Kubik, B J Madden, C G Head, D Harvey, N B Roberts
• Journal: Mayo Clinic proceedings (Mayo Clin Proc) Vol. 73 Issue 4 Pg. 321-8 (Apr 1998) ISSN: 0025-6196 [Print] England
• PMID: 9559035 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glycated Hemoglobin A

Topics

• Adult
• Aged
• Diabetes Mellitus (blood, ethnology)
• Female
• Glycated Hemoglobin (genetics)
• Humans
• Ireland (ethnology)
• Male
• Mass Spectrometry
• Middle Aged
• Scotland (ethnology)