title: Association of HLA-DQ genotype in autoantibody-negative and rapid-onset type 1 diabetes.
abstract: OBJECTIVE
  Some type 1 diabetic patients have a distinct phenotype characterized by the absence of pancreatic autoantibodies and fulminant clinical symptoms at onset, including marked hyperglycemia, severe diabetic ketoacidosis, and normal to near-normal HbA(1c) levels with complete destruction of beta-cells. However, little is known about genetic factors of this distinct subtype of diabetes (fulminant autoantibody-negative type 1 diabetes).
  
  
  METHODS
  We analyzed HLA-DQ genotypes in fulminant autoantibody-negative type 1 diabetes (n = 22) and autoantibody-positive type 1 diabetes (immune-mediated type 1 diabetes, n = 78) recruited from a cohort between 1980 and 2000.
  
  
  RESULTS
  Fulminant autoantibody-negative type 1 diabetes had a significantly high prevalence of the HLA-DQA1*0303-DQB1*0401 haplotype in a homozygous manner (RR 39) or in a heterozygous manner with the HLA-DQA1*0302-DQB1*0303 haplotype (RR 13). In contrast, autoantibody-positive type 1 diabetic patients had a high prevalence of the HLA-DQA1*0302-DQB1*0303 haplotype in a homozygous manner (RR 10) or in a heterozygous manner with the HLA-DQA1*0303-DQB1*0401 haplotype (RR 12).
  
  
  CONCLUSIONS
  Pathogenic roles of genotypic combinations of specific HLA-DQ haplotypes in a homozygous manner are suggested as causative mechanisms of aggressive beta-cell damage in a subtype of autoantibody-negative type 1 diabetes with fulminant clinical features.
authors.affiliation: Third Department of Internal Medicine, Yamanashi Medical University, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Rikako
authors.initials: R
authors.lastname: Koyama
authors.forename: Minoru
authors.initials: M
authors.lastname: Okubo
authors.forename: Toshio
authors.initials: T
authors.lastname: Murase
authors.forename: Masato
authors.initials: M
authors.lastname: Odawara
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
mesh_terms: D001323:Autoantibodies / Q000097:blood; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D010641:Phenotype; D012016:Reference Values
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen