Dna Methylation and Genetic Polymorphisms of Inflammatory and Redox Regulation in Periodontal Disease Activities and Treatment Effectiveness

Periodontal disease is an inflammatory disease. It has been shown that single nucleotide polymorphisms (SNPs) and DNA methylation may contribute to genetic susceptibility to inflammatory and redox regulation in an individual with periodontitis. The hypothesis of this project is that a host's inflammatory response and redox regulation as modified by genetic polymorphism and methylation may affect periodontal disease activities and treatment effectiveness. Therefore, the purpose of this three years project is to explore the association between inflammatory and redox regulation of DNA methylation or genetic polymorphisms in periodontal disease activities and treatment effectiveness. In the first year, this project will aim to explore the association between oxidative stress (Cu/Zn SOD, MnSOD, Catalase, Prx2, Trx1) and inflammatory (IL-1, IL-6, IL-8, TNF-α, MMP8) biomarkers on periodontal disease activities. In the next year, the project will determine whether genetic polymorphism influence the levels of oxidative stress and inflammatory biomarkers as well as periodontal disease activities and treatment effectiveness. In the third year, the project will evaluate the effects of DNA methylation on those biomarkers and periodontal disease activities and treatment effectiveness. This project will collect 300 patients with periodontal disease at Taipei Medical University Hospital. The power ranges 80%-87% on the basis of single nucleotide polymorphism allelic frequency distribution (80%-95%). After the TMU Joint Institutional Review Board has approved the project, all of the subjects provides informed consent before the interview process and specimen collection. Structured questionnaire and specimen collection is completed by standardized personal interview. Saliva is collected by using Saliva-Check kit (GC Corporation, Tokyo, Japan). Salivary oxidative stress (Cu/Zn SOD, MnSOD, Catalase,Prx2, and Trx1) and inflammatory (IL-1, IL-6, IL-8, TNF-α, MMP8) biomarkers are determined by MILLIPLEX MAP Human Oxidative Stress Magnetic Bead Panel kit and Human Cytokine/chemokine Magnetic Bead Panel, respectively (EMD Millipore Corporation, Billerica, MA, USA). DNA extraction from oral swab is used for genetic polymorphism and methylation analysis. Genetic Polymorphism is determined by using real-time PCR. After bisulfite conversion, DNA methylation is determined by using methylation specific real-time PCR. This research will clarify the important roles of periodontal treatment in the relationship among inflammatory response, redox regulation, and genetic polymorphism and methylation. We anticipate the integrated and consecutive project providing invaluable findings to enhance the quality and effectiveness of periodontal treatment.