HSP70-hom gene single nucleotide (+2763 G/A and +2437 C/T) polymorphisms in sarcoidosis

Int J Immunogenet. 2006 Apr;33(2):135-40. doi: 10.1111/j.1744-313X.2006.00584.x.

Abstract

In the present study, two coding polymorphisms within the heat shock protein 70-hom gene (HSP70-hom) were analysed. One hundred and thirty-eight individuals were studied, including 42 Polish patients with sarcoidosis, 13 of which presented with Löfgren's syndrome (LS), and 94 control subjects. Dimorphisms at positions +2763 (A/G) and +2437 (C/T) of the HSP70-hom gene were typed using amplification refractory mutation system and polymerase chain reaction-restriction fragment length polymorphism technique, respectively. A significant prevalence of the HSP(+2437)-C allele and the HSP(+2437)-CC homozygous genotype was observed in patients with sarcoidosis and in those presenting with LS as compared to controls (P < 0.001 in all comparisons made). A majority of HLA-DRB1*03-positive patients with LS were carrying both HSP(+2437)-C and (+2763)-G alleles, and the concomitant presence of these three genetic factors was more frequent among patients with LS as compared to patients without LS (0.54 vs. 0.17, P < 0.05) and controls (0.54 vs. 0.01, P < 0.001). The association of the HSP(+2437)-C allele with sarcoidosis and LS appeared to be independent of the presence of DRB1*03, although this HLA specificity was associated with LS manifestation. The HSP(+2763)-G allele was independently associated with neither sarcoidosis nor LS. However, this HSP(+2763)-G allele was present with either DRB1*03 or HSP(+2437)-C within the same haplotypes in the patients and this might explain the observed prevalence of DRB1*03, HSP(+2437)-C and (+2763)-G in patients with LS. In conclusion, HSP(+2437)-C allele was found as a factor associating with susceptibility to sarcoidosis and LS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • HSP70 Heat-Shock Proteins / genetics*
  • Haplotypes
  • Homozygote*
  • Humans
  • Male
  • Middle Aged
  • Multigene Family
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Sarcoidosis / genetics*
  • Sarcoidosis / immunology
  • Severity of Illness Index
  • Syndrome

Substances

  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HSP70 Heat-Shock Proteins