Association between periodontitis and common variants in the promoter of the interleukin-6 gene
Introduction
Interleukin-6 (IL6) is a cytokine synthesized in response to several inflammatory stimuli by a variety of cells such as macrophages and neutrophils. A role for IL6 in the modulation of inflammatory responses has been hypothesized for inflammatory conditions such as atherosclerosis and rheumatoid arthritis [1], [2]. It is thought that individual variability in the ability to synthesize and release IL6 may modulate the predisposition to a number of inflammatory diseases. Such individual variability seems to be regulated by common nucleotide variations in the gene encoding for IL6, located on chromosome 7p21 [3], [4], [5].
The last 10 years have seen a tremendous research effort in the hunt for genetic factors that may predispose to one of the most common chronic inflammatory diseases in humans, periodontitis. The search initially focused on single nucleotide polymorphisms (SNPs) located in the intereukin-1 (IL-1) gene [6]. More recently, epidemiological studies focusing on the relationship between IL6 SNPs and inflammatory conditions, including periodontitis have flourished. Some studies have reported an association between IL6 −174G>C polymorphism and periodontitis [7], [8], [9]. We have recently reported an association between IL6 SNPs and haplotypes and the presence of aggressive periodontitis (AgP) [10], and of periodontopathogenic bacteria [11]. However, large studies in this respect are still lacking. The aim of this study was to investigate the association between IL6 genotypes and haplotypes and periodontitis, in subjects affected by the most common form of periodontitis (chronic periodontitis, CP) and by the less prevalent aggressive periodontitis (AgP), characterized by faster disease progression in otherwise healthy individuals.
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Materials and methods
All subjects had been referred to the Eastman Dental Hospital (EDH), University College London by general dental practitioners. This sample includes 763 subjects: 231 healthy controls [10], 229 cases diagnosed with aggressive periodontitis [10], and 303 cases diagnosed with chronic periodontitis. All patients gave written informed consent for genetic analyses including IL6 SNPs. The studies had been reviewed and approved by the Eastman/UCLH Joint Ethics Committee.
Results
The demographic characteristics of the subjects who took part in the study are presented in Table 1. The distribution of the genotypes for all of the SNPs studied satisfied Hardy–Weinberg equilibrium in controls and periodontitis patients. A total of 89 genotypes out of 3765 (2.4%) across all subjects for all studied SNPs were not scored because they gave unclear results after repeated analysis. Considerable differences in allele frequencies were detected between Caucasians, Blacks, and Asians
Discussion
Genetic factors determining Interleukin-6 levels have recently emerged as putative predisposing factors to periodontitis and colonization by periodontopathogenic bacteria [7], [10], [11]. The mechanisms for such predisposition may involve an increased promoter activity linked with some IL6 genotypes [3], [4], which may in turn lead to an excessive inflammatory reaction, responsible for periodontal tissue destruction. Recent reports suggest that more than one of the IL6 polymorphic sites are
Acknowledgments
This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. This study was also supported by the Periodontal Research Fund of the Eastman Dental Institute. S.E.H. is supported by the BHF (RG 2005/014).
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