Associations between Interleukin-6 Genetic Polymorphisms and Levels of Autoantibodies to 60-kDa Heat-Shock Proteins

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.

Human anti-60 kD heat shock protein autoantibodies are characterized by basic features of natural autoantibodies

“…the large inter-individual differences, is probably under the strict control and regulation of genetic factors. Our first observation obtained in a healthy Finnish population identified promoter polymorphism of interleukin-6 as one of the underlying regulatory factors (17), and these results were confirmed in a recent independent study (28). Furthermore, epistatic interaction between immunoglobulin GM allotypes and interleukin-6 was also identified in association with increased anti-Hsp60 antibody levels.…”

Interleukin-6 promoter polymorphism (-174 G/C) in Indian patients with chronic periodontitis

“…A number of studies have focused on the role of interleukin-6 genetic polymorphism in inflammatory systemic diseases and conditions (17)(18)(19). There is strong evidence that genetic, as well as environmental factors affect the age of onset, severity, and risk of developing periodontitis (20)(21)(22).…”

Interleukin-6 (IL-6) -174G/C genomic polymorphism contribution to the risk of coronary artery disease in a Chinese population

“…Previous studies have shown that the IL-6 genomic variants is associated with IL-6 levels to the susceptibility to many diseases (Kiszel et al, 2006;Talar-Wojnarowska et al, 2009;Yeh et al, 2010). Talar-Wojnarowska et al (2009) done a study with 97 pancreatic cancer or chronic pancreatitis patients and 50 healthy volunteers, and reported that IL-6 -174G/C gene polymorphism was correlated with circulating IL-6 levels and pathogenesis of pancreatic cancer.…”