title: HLA-DQ haplotypes differ by ethnicity in patients with childhood-onset diabetes.
abstract: OBJECTIVE
  To understand the etiology of childhood-onset diabetes, we examined genetic risk markers, autoantibodies, and β-cell function in a mixed race group of young patients.
  
  
  METHODS
  One hundred and forty-five patients aged 0-17 at diagnosis (54% African American, 22% Caucasian, 16% Latino, 8% mixed-other) were studied at mean duration 6.9 ± 5.7 (range 0.1-28.5) yr, including human leukocyte antigen (HLA)-DQA1-DQB1 genotyping, stimulated C peptide (CP), glutamic acid decarboxylase, and insulinoma-associated antigen 2 antibodies (ABs). Based on no residual β-cell function (CP-) and islet autoantibodies (AB+), 111 patients were classified with type 1 diabetes mellitus (T1DM), 22 were CP+ and AB- and thus considered to have type 2 diabetes mellitus (T2DM), and 12 patients had features of both T1DM and T2DM or mixed phenotype.
  
  
  RESULTS
  Based on the presence of two high-risk HLA-DQA1/B1 haplotypes, 39% of African Americans, 81% of Caucasians, 70% of Latinos, and 67% of mixed-others were at high genetic risk. In patients with T1DM, 41% of African Americans, 80% of Caucasians, 73% of Latinos, and 63% of mixed-others were genetically susceptible. Thirty-one percent of African Americans, including 29% of those with T1DM, could not be characterized because their haplotypes had unknown T1DM associations. These unusual haplotypes comprised 11% in T1DM, 14% in T2DM, and 8% in patients with mixed phenotype.
  
  
  CONCLUSIONS
  Fifty-nine percent of childhood-onset patients with T1DM were identified with high genetic risk based on known HLA-DQA1/B1 associations. Many non-Caucasian patients carry HLA-DQ alleles whose association with T1DM is undetermined. Genetic approaches can provide insights into the etiology and appropriate treatment of childhood-onset diabetes but only if sufficient data are available in diverse ethnic groups.
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA. lipton@uchicago.edu
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Lipton
authors.forename: Melinda
authors.initials: M
authors.lastname: Drum
authors.forename: Siri Atma W
authors.initials: SA
authors.lastname: Greeley
authors.forename: Kirstie K
authors.initials: KK
authors.lastname: Danielson
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
authors.forename: William A
authors.initials: WA
authors.lastname: Hagopian
mesh_terms: D001741:Black or African American / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000208:ethnology* / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D044465:White People / Q000235:genetics
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D005968:Glutamate Decarboxylase