Association of HLA-DQ genotype in autoantibody-negative and rapid-onset type 1 diabetes.
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.
Tanaka
Shoichiro
S
Third Department of Internal Medicine, Yamanashi Medical University, Japan.
Kobayashi
Tetsuro
T
Nakanishi
Koji
K
Koyama
Rikako
R
Okubo
Minoru
M
Murase
Toshio
T
Odawara
Masato
M
Inoko
Hidetoshi
H
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
D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen