Associations between interleukin-6 genetic polymorphisms and levels of autoantibodies to 60-kDa heat-shock proteins.
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.
Kiszel
Petra
P
IIIrd Department of Internal Medicine and Szentágothai János Knowledge Centre, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Fust
George
G
Pessi
Tanja
T
Hurme
Mikko
M
Prohászka
Zoltán
Z
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
D001323:Autoantibodies; D001324:Autoantigens; D018834:Chaperonin 60; D015850:Interleukin-6