HLA associations in insulin-dependent diabetes: search for heterogeneity in different groups of patients from a homogeneous population

Tissue Antigens. 1986 Oct;28(4):237-44. doi: 10.1111/j.1399-0039.1986.tb00489.x.


A total of 317 unrelated Danish patients with insulin-dependent diabetes mellitus (IDDM) have been HLA-DR typed and the antigen and phenotype frequencies compared with those in 1177 unrelated Danish controls. The strong positive associations with DR3 and 4 and the strong negative one with DR2 were confirmed, and the remaining antigens showed a hierarchy from weakly positive to strongly negative associations: DRw9, w8, 1, 5, w6, 7. The study population included various special groups of patients selected in order to study heterogeneity: very early (less than 5 years) and very late (greater than 40 years) onset IDDM, pregnancy-induced IDDM, IDDM nephropathy, and long-term (greater than 40 years) survivors without complications. When comparing these groups, the following minor differences were seen: the DR3,4 phenotype is significantly (p = .02) more frequent in IDDM with onset before age 20 (35%) than in other cases (24%), and in familial IDDM (48%) than in other cases (28%); the frequency of the DR4 antigen was significantly (p = .008) more frequent in long-term survivors (86%) than in other patients (69%), while it was significantly (p = .02) less frequent in IDDM nephropathy (63%) than in long-term survivors. However, apart from the age-at-onset heterogeneity, which was suspected a priori, these differences may be due to chance, and the main conclusion of this study is that the HLA-DR associations in IDDM are indeed extraordinarily homogeneous irrespective of the clinical characteristics at onset and course of the disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Denmark
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / mortality
  • Disease Susceptibility
  • HLA Antigens / analysis*
  • HLA Antigens / immunology
  • HLA-DR Antigens / analysis
  • HLA-DR3 Antigen
  • HLA-DR4 Antigen
  • Histocompatibility Testing
  • Humans
  • Phenotype


  • HLA Antigens
  • HLA-DR Antigens
  • HLA-DR3 Antigen
  • HLA-DR4 Antigen