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  • Title: Tumor necrosis factor-alpha gene promoter methylation in Japanese adults with chronic periodontitis and rheumatoid arthritis.
    Author: Kojima A, Kobayashi T, Ito S, Murasawa A, Nakazono K, Yoshie H.
    Journal: J Periodontal Res; 2016 Jun; 51(3):350-8. PubMed ID: 26247485.
    Abstract:
    BACKGROUND AND OBJECTIVE: Over-expression of tumor necrosis factor-alpha (TNF-α) plays a pathological role in chronic periodontitis (CP) and rheumatoid arthritis (RA), which might be regulated by the epigenetic mechanism. The aim of the present study was to evaluate whether there is a unique methylation profile of the TNF-α gene promoter in blood cells of individuals with CP and RA. MATERIAL AND METHODS: The study participants consisted of 30 Japanese adults with RA (RA group), 30 race-matched adults with CP only (CP group) and 30 race-matched healthy controls (H group). Genomic DNA isolated from peripheral blood was modified by sodium bisulfite and analyzed, by direct sequencing, to investigate DNA methylation of the TNF-α gene promoter region. The level of TNF-α produced in mononuclear cells stimulated with Porphyromonas gingivalis lipopolysaccharide was determined using ELISA. RESULTS: Twelve cytosine-guanine dinucleotide (CpG) motifs were identified in the TNF-α promoter fragment from -343 to +57 bp. The CP group showed a significantly higher methylation rate and frequency at -72 bp than the H group (p < 0.01). The RA group exhibited significantly higher methylation rates at seven CpG motifs (-302, -163, -119, -72, -49, -38 and +10 bp), and significantly higher methylation frequencies at six CpG motifs (-163, -119, -72, -49, -38 and +10 bp), than the H group (p < 0.01 for all comparisons). The levels of TNF-α produced were significantly different between individuals with and without methylation at -163 bp (p = 0.03). CONCLUSION: These results suggest that the hypermethylated status of CpG motifs in the TNF-α gene promoter in blood cells may be unique to Japanese adults with CP and RA.
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