title: HSP70-hom gene single nucleotide (+2763 G/A and +2437 C/T) polymorphisms in sarcoidosis.
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.
authors.affiliation: L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolf Weigl 12, 53-114 Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.forename: K
authors.initials: K
authors.lastname: Koscinska
authors.forename: K
authors.initials: K
authors.lastname: Suchnicki
authors.forename: A
authors.initials: A
authors.lastname: Lange
mesh_terms: D000208:Acute Disease; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012507:Sarcoidosis / Q000235:genetics* / Q000276:immunology; D012720:Severity of Illness Index; D013577:Syndrome
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins