title: HLA-DPB1*0402 protects against type 1A diabetes autoimmunity in the highest risk DR3-DQB1*0201/DR4-DQB1*0302 DAISY population.
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-DQB1*0201/DR4-DQB1*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.
  
  
  METHODS
  We genotyped 457 DR3-DQB1*0201/DR4-DQB1*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 approximately 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 = 0.004) for general population children. Even when the population analyzed is limited to DR3-DQB1*0201/DR4-DQB1*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.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, CO 80045-6511, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Baschal
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Aly
authors.forename: Sunanda R
authors.initials: SR
authors.lastname: Babu
authors.forename: Maria S
authors.initials: MS
authors.lastname: Fernando
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Miao
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Barriga
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: Janelle A
authors.initials: JA
authors.lastname: Noble
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Rewers
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
mesh_terms: D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D005838:Genotype; D006681:HLA-D Antigens; D006682:HLA-DP Antigens / Q000276:immunology*; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000276:immunology*; D059866:HLA-DQ beta-Chains; D006650:Histocompatibility Testing; D006801:Humans; D009679:Nuclear Family; D018570:Risk Assessment; D013534:Survival
chemical_list: D006681:HLA-D Antigens; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen