Aspartic acid at position 57 of the HLA-DQ beta chain is protective against future development of insulin-dependent (type 1) diabetes mellitus.
Insulin-dependent (Type I) diabetes mellitus is a chronic autoimmune disease. From studies in discordant twins and multiplex families a long prediabetic period has been reported. In a population-based program started in 1983, fifteen individuals at possible risk for future Type I diabetes were followed for up to 74 months. Two individuals (13%) developed Type I diabetes. These probands were characterized by the presence of high-level cytoplasmic islet cell antibodies (ICA), complement-fixing ICA, and an impaired first-phase insulin response after intravenous glucose load. Both were homozygous for a high-risk immunogenetic marker of Type I diabetes, i.e., non-Asp at codon 57 of the HLA-DQ beta chain. In all other subjects studied, the immunogenetic marker that confers "dominant resistance", aspartic acid at codon 57, was found. On the basis of our data we conclude that a combination of assays which determine ICA, first-phase insulin release, and HLA-DQB1 polymorphisms will identify individuals with a high probability of developing Type I diabetes at the population level. Conversely, HLA haplotypes positive for aspartic acid seem to confer resistance to the disease.
Boehm
B O
BO
Klinikum der Johann Wolfgang Goethe-Universität, Zentrum der Inneren Medizin, Frankfurt, Main, FRG.
Manfras
B
B
Rosak
C
C
Schöffling
K
K
Trucco
M
M
D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics*; D001323:Autoantibodies / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D013967:Thyroiditis, Autoimmune / Q000235:genetics
D001323:Autoantibodies; D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C057615:HLA-DQbeta antigen; D006684:HLA-DR Antigens; C024211:islet cell antibody; D001224:Aspartic Acid