Hypomethylation of the interleukin-6 promoter in gingival tissue of patients with periodontitis.

Abstract

BACKGROUND DNA methylation may influence cytokine expression and clinical manifestations of periodontitis. This study assessed the interleukin (IL)-6 DNA methylation in gingivae with and without clinical inflammation and its impact on clinical manifestations and cytokine expression. METHODS Sixty-two gingival biopsies (17 from controls and 45 from periodontitis sites) were analyzed. IL-6 protein concentrations were measured using an enzyme-linked immunosorbent assay, and methylation of the IL-6 promoter was analyzed by bisulfite sequencing. At 19 motifs spanning from 1200 to 27 base pairs (bp), the methylation rates for each motif and the overall promoter region were assessed. RESULTS IL-6 concentrations were significantly higher in the periodontitis group than in the control group (135.69 ± 10.24 vs. 65.17 ± 29.18 pg/mL) and were positively correlated with probing depth (PD) and clinical attachment loss (CAL) (r = 0.59 and 0.48, respectively). The overall methylation rate was significantly lower in the disease group (43.97% ± 4.54% vs. 39.54% ± 7.66%) and negatively correlated with PD, CAL, and IL-6 concentrations. Similar trends were also observed for the -74-bp motif: The methylation rate was lower in the periodontitis group than in the control group (8.9% vs. 41.2%, with a relative risk of 0.216), and gingivae with methylation at -74-bp exhibited lower PD and CALs but higher overall methylation rates. CONCLUSION DNA hypomethylation of the IL-6 promoter region, particularly the -74-bp motif, was linked to increased cytokine expression and periodontal clinical signs, suggesting its role in disease progression. PLAIN LANGUAGE SUMMARY This study examined how changes in the interleukin (IL)-6 gene-specifically through a process called DNA methylation-are linked to gum disease (periodontitis) and its symptoms. Sixty-two gum tissue samples were collected: 17 from individuals without gum disease and 45 from those with it. The gum tissues from people with periodontitis showed higher levels of the IL-6 protein, which were associated with more severe gum damage, such as deeper pockets around the teeth and greater loss of attachment. The researchers also found that a part of the IL-6 gene was less methylated in people with gum disease-a change that can lead to increased gene activity. This was especially evident at a specific site in the gene, 74 base pairs from the start. Lower methylation at this site was linked to higher IL-6 levels and more severe symptoms. Overall, the findings suggest that reduced methylation of the IL-6 gene may contribute to the progression of gum disease.