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Åke Lernmark

Principal investigator

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D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus.

Author

  • A M Valdes
  • G Thomson
  • J Graham
  • M Zarghami
  • B McNeney
  • I Kockum
  • A Smith
  • M Lathrop
  • A R Steenkiste
  • J S Dorman
  • J A Noble
  • J A Hansen
  • A Pugliese
  • Åke Lernmark

Summary, in English

Aims/hypothesis: The HLA class II DQB1*0602 allele confers strong dominant protection against type 1 diabetes but protection is not absolute. The aim of this study was to identify markers within the HLA region that differentiate DQB1*0602 haplotypes and show different associations with disease risk.

Methods: We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden.

Results: We found that allele 15 at marker D6S265 (109 kb centromeric of HLA-A) was over-represented among patients carrying DRB1*15, DQB1*0602. A detailed haplotype analysis showed that DRB1*15, DQB1*0602 haplotypes carrying D6S265*15 have a ten-fold higher odds ratio (OR) than those carrying other alleles and thus confer reduced protection [OR D6S265*15=0.186 (95% CI 0.074, 0.472) vs OR D6S265*15−=0.017 (95% CI 0.005, 0.062), p<0.001].

Conclusions/interpretation: Our data support the existence of a locus that modifies the protective effect associated with DQB1*0602. Typing for allele D6S265*15 can identify a less protective DQB1*0602 haplotype, thereby allowing a more accurate prediction of type 1 diabetes risk.

Electronic Supplementary Material: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00125-005-0011-8

Publishing year

2005

Language

English

Pages

2540-2543

Publication/Series

Diabetologia

Volume

48

Issue

12

Document type

Journal article (letter)

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • D6S265
  • DQB1*0602
  • HLA-DQ antigens
  • IDDM
  • Type 1 diabetes mellitus

Status

Published

ISBN/ISSN/Other

  • ISSN: 1432-0428