Genetic susceptibility markers in Danish patients with type 1 (insulin-dependent) diabetes--evidence for polygenicity in man. Danish Study Group of Diabetes in Childhood

Autoimmunity. 1994;19(3):169-78. doi: 10.3109/08916939408995692.


Fifty-five Danish families with two offspring concordant for type 1 diabetes--identified through a nationwide population-based survey, and 57 "true sporadic" cases--matched with familial cases for age at onset, but with no IDDM-affected first-degree relatives and long disease duration, and 110 control subjects were typed for putative genetic susceptibility markers for type 1 diabetes identified from a pathogenetic model. The markers included MHC class I, II and III loci, the manganese superoxide dismutase (MnSOD) locus (chr. 6q), interleukin-1 beta (IL1B), the IL-1 receptor antagonist (IL1RN), and the IL-1 type 1 receptor (IL1RI) loci (each chr. 2q). No significant differences between familial and sporadic cases were found within the MHC region (including the following loci: HLA-DQ, -DR, heat shock protein (HSP) 70, tumour necrosis factor (TNF), HLA-B and -A). In both groups of patients 11% were negative for both DQA1*0301-DQB1*0302 and DQA1*0501-DQB1*0201 genotypes, and 7% of the type 1 diabetics had genotypes unable to encode a susceptibility DQ alpha beta heterodimer. Disease association was found for the IL1RN (p = 0.04) and for the IL1RI (p = 0.03). When comparing controls and only familial cases with type 1 diabetes for the IL1RN polymorphism a difference was observed (p = 0.003). For the IL1B RFLP a trend for difference was observed between familial cases and control subjects (p = 0.046), whereas no differences between sporadic cases and control subjects could be demonstrated neither at the IL1B nor at the IL1RN loci. A difference in the MnSOD pattern was observed between sporadic cases and controls (p = 0.04).

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Alleles
  • Biomarkers
  • Case-Control Studies
  • Child
  • Chromosomes, Human, Pair 2
  • DNA, Satellite / genetics
  • Denmark / epidemiology
  • Diabetes Mellitus, Type 1 / ethnology
  • Diabetes Mellitus, Type 1 / genetics*
  • Disease Susceptibility / ethnology
  • Female
  • Genetic Markers*
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics
  • HSP70 Heat-Shock Proteins / genetics
  • Haplotypes / genetics
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / genetics
  • Lymphotoxin-alpha / genetics
  • Male
  • Middle Aged
  • Polymorphism, Restriction Fragment Length
  • Sialoglycoproteins / genetics
  • Superoxide Dismutase / genetics


  • Biomarkers
  • DNA, Satellite
  • Genetic Markers
  • HLA Antigens
  • HSP70 Heat-Shock Proteins
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Lymphotoxin-alpha
  • Sialoglycoproteins
  • Superoxide Dismutase