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Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with Type 1 (insulin-dependent) diabetes mellitus


Antibodies to glutamic acid decarboxylase, previously known as the 64 kD antigen, appear to be more predictive of Type 1 (insulin-dependent) diabetes mellitus in Caucasoids than other autoantibodies to islet cell antigens. However, seropositivity to glutamic acid decarboxylase is not universal at the onset of Type 1 diabetes and the prevalence in Asians is low compared to Caucasoid patients. This suggests the involvement of multiple pancreatic autoantigens in the Type 1 diabetes autoimmune process or, genetic differences within and between ethnic groups that contribute to the heterogeneous autoimmune response to glutamic acid decarboxylase or both. Alternatively some cases of Type 1 diabetes could have an aetiology unrelated to autoimmunity. This study examined the differential response to glutamic acid decarboxylase according to HLA-DR and -DQ genotypes, as determined by RFLP, in 49 white Australian and 44 Asian patients with Type 1 diabetes. Among Australians heterozygous for HLA-DR3, DR4, 85% were positive for antibodies to glutamic acid decarboxylase, significantly different (p = 0.039) from the prevalence of 48% in patients with at least one HLA-DR antigen other than DR3 or DR4. Also, among Australians, the presence of “low risk” HLA-DQ antigens, namely DQw5, DQw6 or DQw7, reduced the prevalence of antibodies to glutamic acid decarboxylase by 40% (p = 0.064). Among Asians with Type 1 diabetes and with antibodies to glutamic acid decarboxylase, HLA-DR9 was significantly (p = 0.037) increased in frequency, at 63% compared with 22% in those without glutamic acid decarboxylase antibodies, and the presence of a “low risk” HLA-DQ allele reduced the antibody rates by 87% (p = 0.003). These observations may reflect differential genetic/environmental interactions in Type 1 diabetes or differential persistence of glutamic acid decarboxylase antibodies in those with different genetic backgrounds.


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Serjeantson, S.W., Kohonen-Corish, M.R.J., Rowley, M.J. et al. Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35, 996–1001 (1992). https://doi.org/10.1007/BF00401432

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Key words

  • Glutamic acid decarboxylase
  • Type 1 (insulin-dependent) diabetes mellitus
  • HLA-DR
  • HLA-DQ
  • Hong Kong
  • Korea
  • Japan