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

Research output: Contribution to journalLetter


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


  • 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
External organisations
  • University of Washington, Seattle
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • D6S265, DQB1*0602, HLA-DQ antigens, IDDM, Type 1 diabetes mellitus
Original languageEnglish
Pages (from-to)2540-2543
Issue number12
Publication statusPublished - 2005
Publication categoryResearch
Externally publishedYes