Analysis of interleukin-8 gene variants reveals their relative importance as genetic susceptibility factors for chronic periodontitis in the Han population.

Nan Zhang,Haojie Yang,Zufei Feng,Yuehong Xu,Dexing Zhong,Tianxiao Zhang,Bo Zhang,Bao Zhang,Salomon Amar

doi:10.1371/journal.pone.0104436

Abstract

Interleukin (IL)-8, an important chemokine that regulates the inflammatory response, plays an important role in periodontitis. Previous studies indicate that certain IL-8 gene polymorphisms are associated with periodontitis susceptibility in some populations. However, the literature is somewhat contradictory, and not all IL-8 polymorphisms have been examined, particularly in Han Chinese individuals. The aim of this study was to investigate the association of every IL-8 SNP with chronic periodontitis in Han Chinese individuals. We analyzed 23 SNPs with minor allele frequency (MAF)≥0.01, which were selected from 219 SNPs in the NCBI dbSNP and preliminary HapMap data analyses from a cohort of 400 cases and 750 controls from genetically independent Han Chinese individuals. Single SNP, haplotype and gender-specific associations were performed. We found that rs4073 and rs2227307 were significantly associated with chronic periodontitis. Further haplotype analysis indicated that a haplotype block (rs4073-rs2227307-rs2227306) that spans the promoter and exon1 of IL-8 was highly associated with chronic periodontitis. Additionally, the ATC haplotype in this block was increased 1.5-fold in these cases. However, when analyzing the samples by gender, no significant gender-specific associations in IL-8 were observed, similar to the results of haplotype association analyses in female and male subgroups. Our results provide further evidence that IL-8 is associated with chronic periodontitis in Han Chinese individuals. Furthermore, our results confirm previous reports suggesting the intriguing possibilities that IL-8 plays a role in the pathogenesis of chronic periodontitis and that this gene may be involved in the etiology of this condition.

Highlights

Oral Gram-negative bacteria trigger periodontitis, which produces an inflammatory response in a susceptible host [1]
All SNPs were highly polymorphic in both cases and controls, with the exception of 7 SNPs in IL-8, and all SNPs were in Hardy–Weinberg equilibrium (HWE) in both groups
When all of the samples were considered, we observed a significant association for rs4073 (p = 0.028251; odds ratio (OR) = 1.207; 95% CI 1.014–1.437), and rs2227307

Summary

Introduction

Oral Gram-negative bacteria trigger periodontitis, which produces an inflammatory response in a susceptible host [1]. Individual variations in the host’s immune response, which are influenced by environmental and genetic characteristics, account for the predisposition, initiation and progression of periodontitis [2] Environmental factors, such as hormones, diabetes and drugs, modify preexisting periodontal conditions [3]. Several studies have investigated the role of genes and their variants (polymorphisms) in host responses to chronic periodontitis and the progression of this disease [8,9,10,11]. The IL-8 gene, which is located on chromosome 4q12-q13, encodes the IL-8 protein This protein is the most potent chemokine studied to date, and it is responsible for inducing chemotaxis, which is the directed migration of cells to a site of inflammation [17].

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