Analysis of Interleukin-8 Gene Variants Reveals Their Relative Importance as Genetic Susceptibility Factors for Chronic Periodontitis in the Han Population

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.

Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium

“…Likewise, we hypothesized that IL8 rs2227307 and IL12B rs3212227 intronic polymorphisms affect alternative splicing of IL8 and IL12B mRNA and even alter mRNA expression, thereby dysregulating IL8-and IL12-mediated Th1 immune responses against fungal pathogens. In line with these arguments, a number of previous studies have reported associations of these polymorphisms with immune-related diseases (55,56) and infections (57)(58)(59)(60), including IA (45). In particular, we confirmed an association previously reported by Mezger (45).…”

Quantitative Assessment of the Associations Between Interleukin‐8 Polymorphisms and Periodontitis Susceptibility

“…1). Basic characteristics and the scores of study quality assessment of selected articles 15‐26 are all listed in Table 1. Overall, all included studies were of moderate‐to‐high quality, with a mean quality score of 27.4/40 (range: 23 to 30).…”

“…Overall, all included studies were of moderate‐to‐high quality, with a mean quality score of 27.4/40 (range: 23 to 30). Eight studies enrolled non‐smokers, providing an analysis inhibiting the influence of the smoking risk factor 16‐18,21,23‐26 . Six eligible studies mentioned quality control of the genetic analyses, such as mask genotyping, random replication, and validated genotyping accuracy 16,19,20,22,25,26 .…”

“…Eight studies enrolled non‐smokers, providing an analysis inhibiting the influence of the smoking risk factor 16‐18,21,23‐26 . Six eligible studies mentioned quality control of the genetic analyses, such as mask genotyping, random replication, and validated genotyping accuracy 16,19,20,22,25,26 . The control populations of all studies were consistent with HWE except two studies for −251A/T 21,24 and one study for −845T/C 23 …”

“…Nevertheless, subsequent research by Andia et al suggested that this polymorphism may play a protective role in periodontitis risk in non‐smoking Brazilian populations 16 . Until now, results of different studies remain inconsistent rather than conclusive, 17‐26 which was likely due to small sample sizes and low statistical power. To better clarify the associations between polymorphisms in IL‐8 gene and periodontitis susceptibility, this review reports the performance of a quantitative meta‐analysis by collecting and analyzing the published data.…”