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

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

Haplotypes frequency and association analysis.

<p>Significant p-values are in italic bold. Common Haplotypes are shown, if frequency more than 2.5%.</p>1<p>Based on 10000 permutations.</p>2<p>Corrected by Bonferroni.</p>3<p>Based on comparison of frequency distribution of all haplotypes for the combination of SNPs.</p>4<p>Haplotypes in italics are the significant ones in the study.</p

Allele and genotype association analysis in female and male.

<p>OR: odds ratio; CI: confidence interval.</p><p>Significant p values are in italic bold. CI: confidence interval; OR: odds ratio.</p>1<p>P values of the normal chi-square statistics from Monte Carlo stimulation using CLUMP (T1), and significant p values are in italic bold.</p>2<p>OR refers to risk allele odds ratio in cases and controls.</p

Demographic characteristics and clinical parameters of chronic periodontitis and controls.

<p>Demographic characteristics and clinical parameters of chronic periodontitis and controls.</p

Results of logistic regression analysis for susceptibility to chronic periodontitis.

<p>OR: odds ratio; CI: confidence interval.</p><p>Significant p values are in italic bold.</p

Allele and genotype frequency of single SNP association analysis.

<p>OR: odds ratio; CI: confidence interval.</p>1<p>P values of the normal chi-square statistics from Monte Carlo stimulation using CLUMP (T1), and significant p values are in italic bold.</p>2<p>OR refers to risk allele odds ratio in cases and controls.</p