title: Associations between interleukin-6 genetic polymorphisms and levels of autoantibodies to 60-kDa heat-shock proteins.
abstract: OBJECTIVE
  Previously we reported an association between levels of anti-Hsp60 autoantibodies and interleukin-6 (IL-6) -174 SNP in Finnish population. The aim of this study was to investigate the same association in an independent population and to study four recently described SNP in IL-6.
  
  
  METHODS
  313 healthy Hungarian subjects were recruited and genotyped for IL-6 -174(G-->C), -9316(T-->C), -1363(G-->T), +1753(C-->G), +2954(G-->C). IgG antibodies to Hsp60 were measured by ELISA. LD between SNPs was computed by Haploview 3.2 software.
  
  
  RESULTS
  A strong association between IL-6 -174 polymorphism and anti-Hsp60 autoantibody levels was observed. Carriers of -174 CC genotype had significantly lower levels of anti-Hsp60 (p = 0.0052). Eight haplotypes were observed with five SNP-s and autoantibody levels in individuals carrying the most common haplotype (containing allele C of -174) were significantly lower than in all other genotype combinations (p = 0.026).
  
  
  CONCLUSIONS
  Allele C of -174 promoter polymorphism of the IL-6 gene was repeatedly shown to be associated with low anti-Hsp60 autoantibody levels. Strong linkage in the IL-6 gene was observed and the most frequent haplotype containing the -174 C allele was significantly associated with autoantibody levels. Since the -174 SNP of IL-6 is a functional polymorphism, our results indicate for a direct regulatory effect of IL-6 genotypes in the determination of autoantibody levels.
authors.affiliation: IIIrd Department of Internal Medicine and Szentágothai János Knowledge Centre, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Petra
authors.initials: P
authors.lastname: Kiszel
authors.forename: George
authors.initials: G
authors.lastname: Fust
authors.forename: Tanja
authors.initials: T
authors.lastname: Pessi
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology*; D005260:Female; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D018834:Chaperonin 60; D015850:Interleukin-6