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Background and Objective Although chronic periodontitis ( CP) is a multifactorial condition, few studies have investigated the potential association of gene variants with the outcome of periodontal therapy. In a previous study, we reported that variants in the interleukin- 8 ( IL8) gene were associated with CP in a Brazilian population. The aim of this nonrandomized study was to investigate whether genetic susceptibility to CP, conferred by the presence of the IL8 ATC/ TTC haplotype, influences the clinical outcomes of nonsurgical periodontal therapy and the IL-8 protein levels in the gingival crevicular fluid. Material and Methods Forty-one individuals were grouped according to the presence (susceptible to CP; n = 21) or absence (not susceptible to CP; n = 20) of the IL8 ATC/ TTC haplotype. These individuals received nonsurgical periodontal therapy from one periodontist, who was blinded to the genetic status of each patient, and follow up continued for 45 d. The clinical parameters and gingival crevicular fluid samples were collected at baseline and on day 45. The IL-8 levels were determined by an ELISA. The data were subjected to the Mann-Whitney U-test, Wilcoxon and Spearman tests and to multiple logistic-regression analysis. Results No significant differences between patients with or without the IL8 ATC/ TTC haplotype were found for the outcome of nonsurgical periodontal therapy and IL-8 levels. The multiple logistic-regression analysis did not show a statistically significant association between the IL8 haplotype and the variables studied. Conclusion In this longitudinal clinical study, we observed that neither the outcome of nonsurgical periodontal therapy nor the IL-8 levels were influenced by the IL8 ATC/ TTC CP-susceptibility haplotype. Additional studies of CP patients from other ethnic populations are necessary to confirm these results. [ABSTRACT FROM AUTHOR]

Periodontitis is a common chronic inflammatory disease that is initiated by a complex microbial biofilm that poses significant health and financial burdens globally. Porphyromonas gingivalis is a predominant pathogen that maintains chronic inflammatory periodontitis. Toll-like receptors (TLRs) play an important role in periodontitis by recognizing pathogens and maintaining tissue homeostasis. Deficiencies in TLR expression and downstream signaling may reduce the host's innate defenses against pathogens, leading to bacterial persistence and exacerbated inflammation, which are now being better appreciated in disease pathologies. In the case of periodontitis, gingival epithelial cells form the first line of defense against pathogens. Innate immune dysregulation in these cells relates to severe disease pathology. We recently identified a blunted TLR2 expression in certain gingival epithelial cells expressing diminished cytokine signaling upon P. gingivalis stimulation. Upon detailed analysis of the TLR2 promoter CpG Island, we noted higher CpG methylation in this dysregulated cell type. When these cells were treated with DNA methyltransferase inhibitor, TLR2 mRNA and cytokine expression were significantly increased. If TLR2 expression plasmid was ectopically expressed in dysfunctional cells prior to P. gingivalis stimulation, the cytokine expression was increased, confirming the requirement of TLR2 in the P. gingivalis-mediated inflammatory response. We designed a chronic in vitro infection model to test if P. gingivalis can induce DNA methylation in normal gingival epithelial cells that express higher TLR2 upon agonist stimulation. Chronic treatment of normal epithelial cells with P. gingivalis introduced de novo DNA methylation within the cells. In addition, increased DNA methylation was observed in the gingiva of mice infected with P. gingivalis in a periodontitis oral gavage model. Moreover, tissues obtained from periodontitis patients also exhibited differential TLR2 promoter methylation, as revealed by bisulfite DNA sequencing. Taken together, DNA methylation of TLR2 can modulate host innate defense mechanisms that may confer increased disease susceptibility., (© International & American Associations for Dental Research 2014.)