title: 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).
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Haematology, Royal Victoria Hospital, Belfast, Ireland.
authors.forename: G E
authors.initials: GE
authors.lastname: Elder
authors.forename: T R
authors.initials: TR
authors.lastname: Lappin
authors.forename: A B
authors.initials: AB
authors.lastname: Horne
authors.forename: V F
authors.initials: VF
authors.lastname: Fairbanks
authors.forename: R T
authors.initials: RT
authors.lastname: Jones
authors.forename: P C
authors.initials: PC
authors.lastname: Winter
authors.forename: B N
authors.initials: BN
authors.lastname: Green
authors.forename: J D
authors.initials: JD
authors.lastname: Hoyer
authors.forename: T M
authors.initials: TM
authors.lastname: Reynolds
authors.forename: D T
authors.initials: DT
authors.lastname: Shih
authors.forename: D J
authors.initials: DJ
authors.lastname: McCormick
authors.forename: K S
authors.initials: KS
authors.lastname: Kubik
authors.forename: B J
authors.initials: BJ
authors.lastname: Madden
authors.forename: C G
authors.initials: CG
authors.lastname: Head
authors.forename: D
authors.initials: D
authors.lastname: Harvey
authors.forename: N B
authors.initials: NB
authors.lastname: Roberts
mesh_terms: D000328:Adult; D000368:Aged; D003920:Diabetes Mellitus / Q000097:blood* / Q000208:ethnology; D005260:Female; D006442:Glycated Hemoglobin / Q000235:genetics; D006801:Humans; D007494:Ireland / Q000208:ethnology; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D012606:Scotland / Q000208:ethnology
chemical_list: D006442:Glycated Hemoglobin