The distribution of DR4 haplotypes in Sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 loci

Hum Immunol. 1995 Aug;43(4):301-8. doi: 10.1016/0198-8859(95)00042-3.


The contribution of genetic variation at HLA class II loci to the susceptibility to and protection from IDDM was investigated by analyzing the distribution of HLA-DRB1*04 haplotypes in 630 Sardinian newborns and 155 Sardinian IDDM patients. The different RRs and ARs of the various DR4-DQB1*0302 haplotypes, significantly ranging from the strongly associated DRB1*0405, DQB1*0302 to the protective DRB1*0403, DQB1*0302 haplotypes, provides clearcut evidence that the DRB1 locus is crucial in conferring IDDM predisposition or protection. Also, the DQB1 locus influences IDDM predisposition or protection by restricting the disease-positive association to DRB1*0405 haplotypes carrying the susceptibility DQB1*0302 or DQB1*0201 alleles but not the protective DQB1*0301 allele. Haplotype analysis not only suggests that the DRB1 and DQB1 loci influence IDDM risk in the same way, but also that the HLA-linked protection is "dominant" compared with "susceptibility." These results, obtained from a population with one of the highest IDDM incidences in the world, define more clearly the contribution of the various HLA loci to IDDM protection or susceptibility and allow a more precise calculation of AR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics*
  • Genetic Linkage / immunology*
  • HLA-DQ Antigens / genetics*
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics*
  • HLA-DR4 Antigen / genetics*
  • HLA-DRB1 Chains
  • Haplotypes / immunology*
  • Humans
  • Infant
  • Italy


  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DR4 Antigen
  • HLA-DRB1 Chains