Associations between interleukin-6 genetic polymorphisms and levels of autoantibodies to 60-kDa heat-shock proteins

Hum Hered. 2006;62(2):77-83. doi: 10.1159/000096095. Epub 2006 Oct 12.

Abstract

Aims: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / biosynthesis
  • Autoantibodies / blood*
  • Autoantigens / immunology
  • Chaperonin 60 / immunology*
  • Female
  • Genotype
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics*
  • Interleukin-6 / physiology
  • Male
  • Middle Aged
  • Polymorphism, Genetic*

Substances

  • Autoantibodies
  • Autoantigens
  • Chaperonin 60
  • Interleukin-6