||Tumor necrosis factor-alpha gene promoter methylation in Japanese adults with chronic periodontitis and rheumatoid arthritis
Kojima, Anri小島, 杏里
学位の種類: 博士（歯学）. 報告番号: 甲第4148号. 学位記番号: 新大院博（歯）甲第346号. 学位授与年月日: 平成28年3月23日
Journal of Periodontal Research. 2016, 51(3), 350-358.
"Background and Objective: Over-expression of tumor necrosis factor-alpha (TNF-a) 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-a 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-a gene promoter region. The level of TNF-a produced in mononuclear cells stimulated with Porphyromonas gingivalislipopolysaccharide was determined using ELISA. Results: Twelve cytosine–guanine dinucleotide (CpG) motifs were identified in the TNF-a 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 significantlyhigher 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-a 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-a gene promoter in blood cells may be unique to Japanese adults with CP and RA."