Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2540-2543 |
Number of pages | 4 |
Journal | Diabetologia |
Volume | 48 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2005 |
Keywords
- 0602
- D6S265
- DQB1
- HLA-DQ antigens
- IDDM
- Type 1 diabetes mellitus
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism