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- Title
Differential effects of DRB1<sup>*</sup>0301 and DQA1<sup>*</sup>0501-DQB1<sup>*</sup>0201 on the activation and progression of islet cell autoimmunity.
- Authors
Eller, E.; Vardi, P.; McFann, K. K.; Babu, S. R.; Yu, L.; Bugawan, T. L.; Erlich, H. A.; Eisenbarth, G. S.; Fain, P. R.
- Abstract
Autoimmune diabetes shows extreme variation in age of onset and clinical presentation, although most studies have been done in children with the most severe subtype. Disease risk is strongly associated with HLA-DRB1*0301-DQA1*0501-DQB1*0201 (DR3-DQ2), but it has not been possible to separate the effects of the DR and DQ alleles. We have identified a large Bedouin kindred in which a high prevalence of islet autoimmunity is associated with two different DR3 haplotypes, one carrying the usual DQ2 and the other carrying DQA1*0102-DQB1*0502 (DQ5). Results of prospective follow-up studies indicate that DR3 is associated with the initial activation of islet autoimmunity whereas DQ2 is associated with early-onset and severe clinical disease. The association signals map to a 350-kb interval, thus implicating primary effects for DR3 and DQ2. Overall, our results emphasize the importance of prospective genetic studies that examine the full range of variation in the initiation, progression and expression of autoimmune disease.Genes and Immunity (2007) 8, 628–633; doi:10.1038/sj.gene.6364425; published online 30 August 2007
- Publication
Genes & Immunity, 2007, Vol 8, Issue 8, p628
- ISSN
1466-4879
- Publication type
Academic Journal
- DOI
10.1038/sj.gene.6364425