miR-9-1 gene methylation and DNMT3B (rs2424913) polymorphism may contribute to periodontitis

Genetic and epigenetic changes have been associated with periodontitis in various genes; however, little is known about genes involved in epigenetic mechanisms and in oxidative stress. Objective: This study aims to investigate the association of polymorphisms C677T in MTHFR (rs1801133) and −149C→T in DNMT3B (rs2424913), as well as the methylation profiles of MTHFR, miR-9-1, miR-9-3, SOD1, and CAT with periodontitis. The association between polymorphisms and DNA methylation profiles was also analyzed. Methodology: The population studied was composed of 100 nonsmokers of both sexes, divided into healthy and periodontitis groups. Genomic DNA was extracted from the epithelial buccal cells, which were collected through a mouthwash. Polymorphism analysis was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while methylation-specific PCR (MSP) or combined bisulfite restriction analysis techniques were applied for methylation analysis. Results: For DNMT3B, the T allele and the TT genotype were detected more frequently in the periodontitis group, as well as the methylated profile on the miR-9-1 promoter region. There was also a tendency towards promoter region methylation on the CAT sequence of individuals with periodontal disease. Conclusion: The polymorphism −149C→T in DNMT3B (rs2424913) and the methylated profile of the miR-9-1 promoter region are associated with periodontitis

Genetic polymorphisms of genes involved in oxidative stress and inflammatory management in oncopediatric patients with chemo-induced oral mucositis

Oral mucositis (OM) is a painful inflammatory oral condition that affects children who undergo chemotherapy. Oxidative stress is a known OM mediator and pro-inflammatory cytokines contribute to the amplification of the immune response. Objective: To investigate the possible associations of rs4880 (superoxide dismutase 2, SOD2 47 C/T), rs7943316 (catalase, CAT −21 A/T), rs1800629 (tumor necrosis factor α, TNF- α −308 G/A), and rs1800795 (interleukin 6, IL-6 −174 G/C) polymorphisms with chemo-induced OM occurrence and severity in oncopediatric patients. Methodology: We conducted a single-center, observational cross-sectional study with sample collection of oral epithelial cells from 95 children and adolescents with hematological cancers who underwent chemotherapy, followed by genomic DNA extraction. Single-nucleotide polymorphisms (SNPs) were assessed with PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). Demographic data and information concerning OM occurrence were obtained from dental charts of the multidisciplinary oral care team. Information on OM severity was obtained from appropriately-filled Oral Assessment Guide records. Descriptive and inferential statistics were conducted with Student's T test, chi-squared test, and Fisher's exact test, with p≤0.05. Results: The mean age was 10 years-old and most patients were male individuals (57.89%). Female sex was considered a protective factor for OM occurrence (OR=4.83; CI=[1.14; 16.57]). The AA genotype for CAT was the most frequent amongst individuals with severe OM (p=0.04). The GA genotype for TNF- α was the most frequent amongst individuals without severe OM (p=0.03). For SOD2 and IL-6 , the most frequent genotypes were CT and GG respectively for all groups (p>0.05). Conclusion:The AA genotype for CAT −21 A/T was a tendency among the group with severe OM. Data on TNF- α −308 G/A were inconclusive. No associations were detected for SOD2 47 C/T and IL-6 −174 G/C polymorphisms in oncopediatric patients with chemo-induced oral mucositis

DNMT3B (rs2424913) polymorphism is associated with systemic lupus erythematosus alone and with co-existing periodontitis in a Brazilian population

The association between Periodontitis and Systemic Lupus Erythematosus (SLE) has been primarily based on their similar pathophysiology and both are associated with genetic polymorphisms. Objectives: To investigate an association between the methylation-related gene polymorphisms DNMT3B (rs2424913) and MTHFR (rs1801133) to Systemic Lupus Erythematosus (SLE) and Periodontitis. Methodology: In total, 196 individuals of all genders aged 24 to 60 years old were allocated into four groups based on their systemic and periodontal status, namely: Healthy control (n=60), periodontitis (n=51), SLE (n=47), and SLE + periodontitis (n=38). Individuals with SLE were stratified according to disease activity (SLEDAI) in inactive or active. We performed polymorphism analysis using PCR-RFLP with genomic DNA from mouthwash. We analyzed data using Fisher’s Exact, Chi-square test, and regression models. Results: Periodontal status were similar in subjects with periodontitis alone and combined with SLE. SLE patients with periodontitis had a longer SLE diagnosis than SLE only (p=0.001). For DNMT3 B polymorphism, the periodontitis, SLE, and Inactive SLE + periodontitis groups showed a higher frequency of T allele and TT genotypes compared to healthy controls (p<0.05). Regression analyses showed that the TT genotype is a strong risk factor for periodontitis (OR=4.53; CI95%=1.13–18.05) and also for SLE without periodontitis (OR=11.57; CI95%=3.12–42.84) and SLE with periodontitis (OR=5.27; CI95%=1.25–22.11) when compared to control. Conclusion: SLE patients with periodontitis had a longer length of SLE diagnosis. The DNMT3B (rs2424913) polymorphism was associated with periodontitis and SLE alone or combined with periodontitis. Our study contributes to understanding the genetic mechanisms involved in periodontitis and SLE susceptibility

Contribution of DNA methylation to the pathogenesis of Sjögren's syndrome: A review

Sjögren’s syndrome (SS) is a chronic systemic disease characterised by salivary and lacrimal gland dysfunction with severe implications for the well-being of bearing individuals. Although its origin has not yet been fully elucidated, it is known that genetic, environmental, and epigenetic factors are important contributors to the pathogenesis of this syndrome. DNA methylation is a relevant, widely studied epigenetic factor that is possibly related to the establishment of SS. The aim of the present study was to perform a systematic review of the literature to compile studies on the contribution of DNA methylation to the pathogenesis of SS. A literature search was performed in 4 databases (PubMed, Web of Science, Lilacs, and Scopus) using previously selected Medical Subject Headings (MESH) descriptors, and article selection considered observational studies only. After a full-text reading of the selected articles, 15 studies were in accordance with the eligibility criteria for data extraction. Methylation detection approaches included global methylation, genome-wide assessment of differentially methylated regions, and site-specific methylation. Fourteen articles reported associations of DNA methylation profiles in SS patients, both globally and in several genes in salivary glands and blood cells. Thus, DNA methylation may contribute to the pathogenesis of SS. The findings reinforce the importance of epigenetic markers in the dynamics of SS and may direct efforts toward the development of new diagnostic and therapeutic approaches

UV Radiation and Its Relation to DNA Methylation in Epidermal Cells: A Review

DNA methylation is the most studied epigenetic mark, and it can be altered by environmental factors. Among these factors, ultraviolet radiation (UV) is little explored within this context. While the relationship between UV radiation and DNA mutations is clear, little is known about the relationship between UV radiation and epimutations. The present study aimed to perform a literature review to determine the influence of artificial or natural (solar) UV radiation on the global and site-specific methylation profile of epidermal cells. A systematic review of the literature was carried out using the databases PubMed, Scopus, Cochrane, and Web of Science. Observational and intervention studies in cultured cells and animal or human models were included. Most studies showed a relationship between UV radiation and changes in the methylation profile, both global and site-specific. Hypermethylation and hypomethylation changes were detected, which varied according to the studied CpG site. In conclusion, UV radiation can alter the DNA methylation profile in epidermal cells derived from the skin. These data can be used as potential biomarkers for environmental exposure and skin diseases, in addition to being targets for treatments. On the other hand, UV radiation (phototherapy) can also be used as a tool to treat skin diseases. Thus, the data suggest that epigenetic homeostasis can be disrupted or restored by exposure to UV radiation according to the applied wavelength

DNA Methyltransferase Genes Are Associated with Oral Mucositis and Creatinine Levels in Oncopediatric Patients

The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) and the DNA methylation profiles of the DNA methyltransferase (DNMT) gene family with oral mucositis in children and adolescents with hematologic malignancies treated with methotrexate (MTX®). The population was comprised of healthy and oncopediatric patients aged between 4 and 19 years. An evaluation of oral conditions was performed using the Oral Assessment Guide. Demographic, clinical, hematological, and biochemical data were obtained from medical records. Genomic DNA extracted from oral mucosal cells was used for the analysis of polymorphisms in DNMT1 (rs2228611), DNMT3A (rs7590760), and DNMT3B (rs6087990) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique (n = 102) and for DNA methylation using the methylation-specific PCR (MSP) technique (n = 85). The allele and genotypic frequencies of SNPs did not reveal any differences between patients with or without oral mucositis. An increase in the methylation frequency for DNMT1 in patients recovered from mucositis was detected. The DNMT3A methylated profile associated with the CC genotype (SNP rs7590760) appeared to be connected to higher values of creatinine. In addition, the DNMT3B unmethylated profile associated with the CC genotype (SNP rs6087990) appeared to be connected with higher values of creatinine. We conclude that the DNMT1 methylation profile is associated with the post-mucositis period and that the genetic and epigenetic profiles of DNMT3A and DNMT3B are associated with creatinine levels