HLA-DRB1*0403 is associated with dominant protection against IDDM in the general Dutch population and subjects with high-risk DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype

Tissue Antigens. 1999 Jul;54(1):88-90. doi: 10.1034/j.1399-0039.1999.540110.x.


Insulin-dependent (Type 1) diabetes mellitus (IDDM) is a genetically controlled T-cell mediated autoimmune disease. Recently, subtyping of HLA-DRB1*04 identified the HLA-DRB1*0403 allele to be associated with protection in Caucasoids with the highest risk heterozygous genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201. Some studies confirmed this finding, but other reports were not consistent with a dominantly protective trait. We here report the frequency of HLA-DRB1*0403 in a large cohort (n=200) of Dutch patients with IDDM, their first-degree family members (n=370), and random controls (n=420) of the general population in The Netherlands. We found that HLA-DRB1*0403 is strongly associated with dominant protection against development of IDDM in unrelated subject, even in the context of the highest risk HLA-DQ phenotypes and HLA-DR4-DQB1*0302 (P < 0.0001).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Denmark / epidemiology
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • HLA-DQ Antigens / genetics*
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Humans
  • Risk Factors


  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains