Genetic heterogeneity of insulin-dependent (type I) diabetes mellitus: evidence from a study of extended haplotypes

Am J Hum Genet. 1984 Sep;36(5):1015-23.


Two hundred subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were typed for HLA-B, HLA-DR, and properdin factor B (Bf). HLA and Bf antigen and haplotype frequencies in subjects were compared with control frequencies derived from the 8th HLA Workshop. Frequencies of extended haplotypes (defined by B-Bf-DR alleles on a chromosome) were also contrasted with control frequencies. Significant positive associations between IDDM and HLA-B8, DR3, DR4, BfS, and BfF1 were confirmed, as were significant negative associations between IDDM and HLA-B7, DR2, DR5, DR7, and BfF. One haplotype (B7-BfS-DR2) exhibited significant negative association, while five haplotypes (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4) exhibited significant positive associations with IDDM. In this sample, 64% of all probands carried at least one of the high-risk haplotypes. In conclusion, the occurrence of five "high-risk" haplotypes associated with IDDM provides evidence for previously undocumented genetic heterogeneity and suggests that possibly more than two HLA-region genes may be involved in IDDM susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Child
  • Child, Preschool
  • Complement Factor B / genetics
  • Diabetes Mellitus, Type 1 / genetics*
  • Disease Susceptibility
  • Female
  • Gene Frequency
  • Genetic Variation
  • HLA Antigens / genetics
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Risk


  • HLA Antigens
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II
  • Complement Factor B