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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
  • Swedish Childhood Study Group, Diabetes Incidence in Sweden Study Group, Type 1 Diabetes Component of the 13th International Histocompatibility Working Group
Publishing year: 2005
Language: English
Pages: 2540-2543
Publication/Series: Diabetologia
Volume: 48
Issue: 12
Document type: Journal article (letter)
Publisher: Springer

Abstract 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

Keywords

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

Other

Published
  • ISSN: 1432-0428
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

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+46 70 616 47 79

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Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00