A Kojima1, T Kobayashi1,2, S Ito3, A Murasawa3, K Nakazono3, H Yoshie1. 1. Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 2. General Dentistry and Clinical Education Unit, Niigata University Medical and Dental Hospital, Niigata, Japan. 3. Niigata Rheumatic Center, Shibata, Japan.
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.
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 gingivalislipopolysaccharide 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.
Authors: P-J Almiñana-Pastor; M Boronat-Catalá; P Micó-Martinez; C Bellot-Arcís; A Lopez-Roldan; F-M Alpiste-Illueca Journal: Med Oral Patol Oral Cir Bucal Date: 2019-09-01
Authors: Stella Aslibekyan; Golareh Agha; Elena Colicino; Anh N Do; Jari Lahti; Symen Ligthart; Riccardo E Marioni; Carola Marzi; Michael M Mendelson; Toshiko Tanaka; Matthias Wielscher; Devin M Absher; Luigi Ferrucci; Oscar H Franco; Christian Gieger; Harald Grallert; Dena Hernandez; Tianxiao Huan; Stella Iurato; Roby Joehanes; Allan C Just; Sonja Kunze; Honghuang Lin; Chunyu Liu; James B Meigs; Joyce B J van Meurs; Ann Zenobia Moore; Annette Peters; Holger Prokisch; Katri Räikkönen; Wolfgang Rathmann; Michael Roden; Katharina Schramm; Joel D Schwartz; John M Starr; André G Uitterlinden; Pantel Vokonas; Melanie Waldenberger; Chen Yao; Degui Zhi; Andrea A Baccarelli; Stefania Bandinelli; Ian J Deary; Abbas Dehghan; Johan Eriksson; Christian Herder; Marjo-Riitta Jarvelin; Daniel Levy; Donna K Arnett Journal: JAMA Cardiol Date: 2018-06-01 Impact factor: 14.676