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

Diabetologia. 2005 Dec;48(12):2540-3. doi: 10.1007/s00125-005-0011-8. Epub 2005 Nov 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • Chromosome Mapping
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / prevention & control
  • Female
  • Genetic Predisposition to Disease*
  • HLA-DQ Antigens / genetics*
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Haplotypes / genetics*
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Microsatellite Repeats*
  • Middle Aged
  • Odds Ratio
  • Predictive Value of Tests
  • Risk
  • Sweden / epidemiology


  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Membrane Glycoproteins