Diabetologia

, Volume 36, Issue 3, pp 252–257

Both DQA1 and DQB1 genes are implicated in HLA-associated protection from type 1 (insulin-dependent) diabetes mellitus in a British Caucasian population

  • D. A. Cavan
  • K. H. Jacobs
  • M. A. Penny
  • M. A. Kelly
  • C. Mijovic
  • D. Jenkins
  • J. A. Fletcher
  • A. H. Barnett
Originals

DOI: 10.1007/BF00399959

Cite this article as:
Cavan, D.A., Jacobs, K.H., Penny, M.A. et al. Diabetologia (1993) 36: 252. doi:10.1007/BF00399959

Summary

Inherited susceptibility to Type 1 (insulin-dependent) diabetes mellitus is partly determined by HLA genes. It has been suggested that protection from disease may be conferred by HLA-DQB1 genes which encode molecules with aspartate at position 57. We investigated the contributions of HLA-DRB1, DQA1 and DQB1 genes to protection from disease. Restriction fragment length polymorphism and sequence specific oligonucleotide analysis in 156 British Caucasian Type 1 diabetic and 116 control subjects showed protection from disease was associated with DR2, DRw6 and DR7 haplotypes. The most protective DQA1 allele was DQA1*0102 which occurred on both DR2 and DRw6 haplotypes. The DQB1 alleles DQB1*0303, DQB1*0602 and DQB1*0603 were associated with protection, as was DQB1*0604, which encodes an Asp-57 negative DQβmolecule. Heterozygosity for both protective and predisposing HLA markers was reduced in diabetic compared with control subjects. We conclude that both DQA1 and DQB1 genes are implicated in HLA-associated protection from Type 1 diabetes in this British Caucasian population. The overall structure of the DQ heterodimer is critical and DQβ-Asp 57 is of secondary importance in determining protection from disease. The effect of protective HLA types may predominate over that of predisposing markers.

Key words

Type 1 (insulin-dependent) diabetes mellitus HLA genes protection 

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • D. A. Cavan
    • 1
    • 2
  • K. H. Jacobs
    • 1
  • M. A. Penny
    • 1
  • M. A. Kelly
    • 1
  • C. Mijovic
    • 1
  • D. Jenkins
    • 1
  • J. A. Fletcher
    • 1
  • A. H. Barnett
    • 1
  1. 1.Department of MedicineUniversity of Birmingham and East Birmingham HospitalBirminghamUK
  2. 2.Department of MedicineQueen Elizabeth HospitalBirminghamUK

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