Association between periodontitis and common variants in the promoter of the interleukin-6 gene

Abstract

We recently reported an association between interleukin-6 (IL6) polymorphisms (SNPs) and haplotypes and aggressive periodontitis (AgP). The aim of this study was to investigate this association in a larger cohort of subjects, affected by either aggressive or chronic periodontitis. Five IL6 SNPs were analyzed in 765 subjects (167 generalized aggressive periodontitis, 57 localized aggressive, 310 chronic periodontitis and 231 periodontally healthy). Among Caucasians (n = 454) there were moderate associations for −1363T allele (p = 0.011) and for −174GG and −1363GG genotypes with diagnosis of periodontitis (respectively, p = 0.044, OR = 1.6, 95% CI = 1.0–2.4, and p = 0.017, OR = 1.8, 95% CI = 1.1–2.8, adjusted for age, gender and smoking). Haplotypes containing the −174G>C, −1363G>T and −1480C>G polymorphisms were associated with diagnosis of periodontitis (p = 0.02). Subgroup analysis by disease phenotype showed associations for the localized AgP (LAgP) group and −1480C>G and −6106A>T SNPs (p = 0.007 and 0.010, respectively). Among Caucasians the genotypes IL6 −1480 CC and −6106 TT increased the adjusted OR for LAgP (OR = 3.09 and 2.27, respectively). This study supports the hypothesis that IL6 polymorphisms and haplotypes are moderately associated with periodontitis, possibly acting through influencing tissue levels of IL6. This association is stronger for LAgP than for other periodontal disease phenotypes.

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.