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- Title
HLA-DPB1*0402 Protects Against Type 1A Diabetes Autoimmunity in the Highest Risk DR3-DQB1*0201/DR4-DQB1*0302 DAISY Population.
- Authors
Baschal, Erin E.; Aly, Theresa A.; Babu, Sunanda R.; Fernando, Maria S.; Yu, Liping; Miao, Dongmei; Barriga, Katherine J.; Norris, Jill M.; Noble, Janelle A.; Erlich, Henry A.; Rewers, Marian J.; Eisenbarth, George S.
- Abstract
OBJECTIVE--A major goal in genetic studies of type 1A diabetes is prediction of anti-islet autoimmunity and subsequent diabetes in the general population, as >85% of patients do not have a first-degree relative with type 1A diabetes. Given prior association studies, we hypothesized that the strongest candidates for enhancing diabetes risk among DR3-DQBI*0201/DR4-DQBI*0302 individuals would be alleles of DP and DRB1*04 subtypes and, in particular, the absence of reportedly protective alleles DPB1*0402 and/or DRB1*0403. RESEARCH DESIGN AND METHODS--We genotyped 457 DR3-DQBI*0201/DR4-DQBI*0302 Diabetes Autoimmunity Study of the Young (DAISY) children (358 general population and 99 siblings/offspring of type 1 diabetic patients) at the DPB1, DQB1, and DRB1 loci using linear arrays of immobilized sequence-specific oligonucleotides, with direct sequencing to differentiate DRB1*04 subtypes. RESULTS--By survival curve analysis of DAISY children, the risk of persistently expressing anti-islet autoantibodies is ∼55% for relatives (children with a parent or sibling with type 1 diabetes) in the absence of these two protective alleles vs. 0% (P = 0.02) with either protective allele, and the risk is 20 vs. 2% (P = 0.000) for general population children. Even when the population analyzed is limited to DR3-DQBI*0201/DR4-DQBI*0302 children with DRB1*0401 (the most common DRB1*04 subtype), DPB1*0402 influences development of anti-islet autoantibodies. CONCLUSIONS--The ability to identify a major group of general population newborns with a 20% risk of anti-islet autoimmunity should enhance both studies of the environmental determinants of type 1A diabetes and the design of trials for the primary prevention of anti-islet autoimmunity. Diabetes 56: 2405-2409, 2007
- Subjects
DIABETES in children; DIABETES risk factors; AUTOIMMUNITY; ISLANDS of Langerhans; OLIGONUCLEOTIDES; AUTOANTIBODIES
- Publication
Diabetes, 2007, Vol 56, Issue 9, p2405
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db07-0029