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Diabetologia. 2005 Dec;48(12):2540-3. Epub 2005 Nov 18.

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

Author information

1
Department of Integrative Biology, University of California, Berkeley, CA, USA.

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.

PMID:
16320082
DOI:
10.1007/s00125-005-0011-8
[Indexed for MEDLINE]

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