Polymorphic analysis of the human MHC-linked heat shock protein 70 (HSP70-2) and HSP70-Hom genes in insulin-dependent diabetes mellitus (IDDM)

Scand J Immunol. 1993 Nov;38(5):491-5. doi: 10.1111/j.1365-3083.1993.tb02593.x.


In the present study we characterized the frequencies of two polymorphisms within the MHC-linked heat shock protein (HSP) 70 genes in patients with insulin-dependent diabetes mellitus (IDDM) (n = 114) and healthy control individuals (n = 110). Significant differences in genotype and allelic frequencies were observed for both polymorphisms between randomly selected patients and controls. However, for the HSP70-2 polymorphisms this was solely due to linkage disequilibrium with DR3. The rate HSP70-Hom 2-allele was significantly more frequent in controls than in patients. It showed strong association with certain tumour necrosis factor (TNF) (class III) and HLA-B and -A (class I) alleles independent of HLA-DQ and -DR alleles. By typing 257 individuals from 55 IDDM multiple-case families two extended MHC-haplotypes, including class II-, TNF- and class I-markers, carrying the rare HSP70-Hom allele were defined. One was only transmitted to diabetic offspring, whereas the other was only transmitted to unaffected offspring. The functional implication of the polymorphism in the heat shock-inducible HSP70-2 gene was analysed by studying HSP70-2 mRNA expression after heat shock in peripheral blood mononuclear cells from individuals with different HSP70-2 genotypes. Preliminary data showed that individuals homozygous for the PstI 8.5-kb allele consistently had slightly lower expression than heterozygous and 9.0-kb homozygous individuals.

MeSH terms

  • Adult
  • Alleles
  • Base Sequence
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Gene Expression
  • Gene Frequency
  • Genotype
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / immunology
  • Histocompatibility Testing
  • Humans
  • Major Histocompatibility Complex / genetics*
  • Major Histocompatibility Complex / immunology
  • Male
  • Molecular Sequence Data
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • RNA, Messenger / analysis
  • Random Allocation


  • Heat-Shock Proteins
  • RNA, Messenger