In evaluating the pathogenesis of periodontal diseases, the diagnostic potential of gingival crevicular fluid has been extensively explored during the last twenty years, from initially just ...confirming health and disease states to more recently investigating it as a potential prognostic tool. As host susceptibility is a critical determinant in periodontal disease pathogenesis, the inflammatory mediator levels present in gingival crevicular fluid represent relevant risk indicators for disease activity. Considerable work has been carried out to identify the many different cytokine inflammatory pathways and microbial stimuli that are associated with periodontal disease pathogenesis. Now, ‘omics’ approaches aim to summarize how these pathways interact and probably converge to create critical inflammatory networks. More recently, gingival crevicular fluid metabolomics appears promising as an additional diagnostic method. Biofilm structure and the host inflammatory response to the microbial challenge may induce specific inflammatory signatures. Host genetics and epigenetics may also modulate microbial colonization, adding to the multiplicity of potential causal pathways. Omics analyses of gingival crevicular fluid, measuring microbial and host interactions in association with the onset and progression of periodontal diseases, still show the potential to expand the landscape for the discovery of diagnostic, prognostic and therapeutic markers.
The
(
) gene encodes a transcription factor involved in the regulation of complex metabolic and inflammatory diseases. We investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of ...the
gene could contribute with susceptibility to develop periodontitis alone or together with type 2 diabetes mellitus (T2DM). Moreover, we evaluated the gene-phenotype association by assessing the subjects' biochemical and periodontal parameters, and the expression of
and other immune response-related genes. We examined 345 subjects with a healthy periodontium and without T2DM, 349 subjects with moderate or severe periodontitis but without T2DM, and 202 subjects with moderate or severe periodontitis and T2DM.
SNPs rs12495364, rs1801282, rs1373640, and rs1151999 were investigated. Multiple logistic regressions adjusted for age, sex, and smoking status showed that individuals carrying rs1151999-GG had a 64% lower chance of developing periodontitis together with T2DM. The CCGT haplotype increased the risk of developing periodontitis together with T2DM. The rs1151999-GG and rs12495364-TC were associated with reduced risk of obesity, periodontitis, elevated triglycerides, and elevated glycated hemoglobin, but there was no association with gene expression. Polymorphisms of the
gene were associated with developing periodontitis together with T2DM, and with obesity, lipid, glycemic, and periodontal characteristics.
Aim
Several papers have considered the potential relationship between periodontitis and lipid parameters. The present systematic review, meta‐analysis and meta‐regression studies focused on ...investigating whether serum lipid parameter levels were elevated in patients with periodontal disease (PD; without altered systemic conditions) in comparison with periodontally healthy subjects.
Materials and Methods
Eligible studies were those with data about serum lipid parameter levels in non‐smoking subjects with and without chronic periodontitis, who are generally healthy and not taking any medication for dyslipidaemia. Mean differences and 95% confidence intervals for total cholesterol, triglycerides, low‐density lipoprotein (LDL) cholesterol and high‐density lipoprotein (HDL) cholesterol were obtained from all the selected studies.
Results
A total of 19 publications were included for meta‐analysis. Participants with chronic periodontitis presented significantly higher serum levels of LDL and triglycerides (p = .003 and p < .0001, respectively). The total cholesterol was higher in the PD group, but without significant difference in comparison with healthy participants. Significantly (p = .0005) lower HDL serum levels were found in patients with chronic periodontitis than in healthy subjects.
Conclusions
Even considering the limitations of this meta‐analysis, it is suggested that PD is significantly associated with reduction in HDL and elevation of LDL and triglyceride concentrations. This analysis supports the rationale that periodontal disease is associated with lipid metabolic control.
Transcription factors of the basic leucine zipper (bZIP) family control important processes in all eukaryotes. In plants, bZIPs are master regulators of many central developmental and physiological ...processes, including morphogenesis, seed formation, abiotic and biotic stress responses. Modulation of the expression patterns of bZIP genes and changes in their activity often contribute to the activation of various signaling pathways and regulatory networks of different physiological processes. However, most advances in the study of plant bZIP transcription factors are related to their involvement in abiotic stress and development. In contrast, there are few examples of functional research with regard to biotic stress, particularly in the defense against pathogens. In this review, we summarize the recent progress revealing the role of bZIP transcription factors in the biotic stress responses of several plant species, from Arabidopsis to cotton. Moreover, we summarize the interacting partners of bZIP proteins in molecular responses during pathogen attack and the key components of the signal transduction pathways with which they physically interact during plant defense responses. Lastly, we focus on the recent advances regarding research on the functional role of bZIPs in major agricultural cultivars and examine the studies performed in this field.
In COPD patients, fatal and non-fatal respiratory-related events are influenced by age, severity of respiratory disease, and comorbidities.
Analyze the effects of edentulism, periodontal disease and ...systemic biomarkers of inflammation on the occurrence of serious fatal and non-fatal respiratory-related events among subjects with COPD.
Cases were identified from Dental Atherosclerosis Risk in Communities study. Edentulism was defined as study participants without any natural teeth or implants. Participants with one or more natural teeth (comprising 11,378 subjects) were studied as dentate subjects. Periodontal disease status among dentate individuals was determined using the consensus definitions published by the joint Center for Disease Control/American Association of Periodontology working group). Adjusted Hazard Models are developed to evaluate the relationship between edentulism/periodontal disease and COPD Related Events. Models were then stratified by GOLD Stage I, II and III/IV. Serum biomarkers were also evaluated to explore the effect of systemic inflammation.
A statistically significant association was found between oral health status and COPD-related events, even adjusting for conditions such as hypertension, smoking and diabetes. Edentulous individuals who had been diagnosed with COPD had a higher incidence and were at greater risk of having a COPD related event (hospitalization and death) than individuals who had teeth and whose mouths had healthy periodontal status. However, being edentulous did not convey excess risk for COPD-related events for those study participants who were classified as GOLD III/IV at baseline. Finally, we showed that individuals who had levels of serum IL-6 in the highest two quartiles were at even higher risk for COPD-related events.
These findings suggest that the risk for COPD-related events after adjusting for potential confounders may be attributable to both edentulism and elevated serum IL-6 levels.
Epigenetics as a modifiable risk factor in periodontal diseases has been investigated in light of the current knowledge of how chronic infection and inflammation can affect gene-specific epigenetic ...reprogramming in periodontal tissues. Epigenomic programming might be particularly sensitive to environmental influences, and a combination of physiological stressors and environmental exposures appears to affect the epigenomic program acquired by a cell during differentiation and throughout the cellular lineage lifespan. Viral and bacterial infections can establish several types of epigenetic modifications, which sometimes engage in a complex epigenetic crosstalk also reflecting in the establishment and progress of periodontal diseases. The inflammatory and metabolic states of the periodontal tissues are driven by the infectious stimuli, and the magnitude of the cellular and molecular signature response is further dictated by the host genetic and epigenetic traits associated with various systemic exposures, including smoking, obesity and diabetes/hyperglycemia. This review discusses the advances in epigenetics, focusing on the role of DNA methylation in the pathogenesis of periodontal disease and the potential of epigenetic therapy.
Rethinking Periodontal Inflammation Offenbacher, Steven; Barros, Silvana P.; Beck, James D.
Journal of periodontology,
August 2008, Letnik:
79, Številka:
8
Journal Article, Conference Proceeding
Recenzirano
Clinical signs and symptoms, as well as medical and dental history, are all considered in the clinical determination of gingival inflammation and periodontal disease severity. However, the “biologic ...systems model” highlights that the clinical presentation of periodontal disease is closely tied to the underlying biologic phenotype. We propose that the determination and integration of subject‐level factors, microbial composition, systemic immune response, and gingival tissue inflammatory mediator responses will better reflect the biology of the biofilm–gingival interface in a specific patient and may provide insights on clinical management. Disease classifications and multivariable models further refine the biologic basis for the increasing severity of periodontal disease expression. As such, new classifications may better identify disease‐susceptible and treatment–non‐responsive individuals than current classifications that are heavily influenced by probing and attachment level measurements alone. New data also suggest that the clinical characteristics of some complex diseases, such as periodontal disease, are influenced by the genetic and epigenetic contributions to clinical phenotype. Although the genetic basis for periodontal disease is considered imperative for setting an inflammatory capacity for an individual and, thus, a threshold for severity, there is evidence to suggest an epigenetic component is involved as well. Many factors long associated with periodontitis, including bacterial accumulations, smoking, and diabetes, are known to produce strong epigenetic changes in tissue behavior. We propose that we are now able to rethink periodontal disease in terms of a biologic systems model that may help to establish more homogeneous diagnostic categories and can provide insight into the expected response to treatment.
There is no agnostic GWAS evidence for the genetic control of IL-1β expression in periodontal disease. Here we report a GWAS for "high" gingival crevicular fluid IL-1β expression among 4910 ...European-American adults and identify association signals in the IL37 locus. rs3811046 at this locus (p = 3.3 × 10
) is associated with severe chronic periodontitis (OR = 1.50; 95% CI = 1.12-2.00), 10-year incident tooth loss (≥3 teeth: RR = 1.33; 95% CI = 1.09-1.62) and aggressive periodontitis (OR = 1.12; 95% CI = 1.01-1.26) in an independent sample of 4927 German/Dutch adults. The minor allele at rs3811046 is associated with increased expression of IL-1β in periodontal tissue. In RAW macrophages, PBMCs and transgenic mice, the IL37 variant increases expression of IL-1β and IL-6, inducing more severe periodontal disease, while IL-37 protein production is impaired and shows reduced cleavage by caspase-1. A second variant in the IL37 locus (rs2708943, p = 4.2 × 10
) associates with attenuated IL37 mRNA expression. Overall, we demonstrate that IL37 variants modulate the inflammatory cascade in periodontal disease.
Background
Bioinformatic tools and genome‐wide association studies (GWAS) have led to comprehensive identification of single nucleotide polymorphisms (SNPs) associated with periodontitis in diverse ...populations. Here we aimed to detect and validate the association of seven SNPs as genetic markers of susceptibility to periodontitis in a Brazilian population.
Methods
This case‐control study assessed complete periodontal parameters of 714 subjects with periodontal status classified as healthy/mild periodontitis (n = 356) and moderate/severe periodontitis (n = 358). Genotyping for rs187238, rs352140, rs1360573, rs2521634, rs3811046, rs3826782, and rs7762544 SNPs were evaluated. Genetic‐phenotype associations, and sex or smoking effects of SNPs on periodontitis were tested using multiple logistic regressions adjusted for covariates.
Results
The rs2521634‐AA (close to NPY gene) presented increased risk for severe periodontitis (OR = 2.34; 95% CI = 1.19–4.59). The rs3811046‐GG (IL37 gene) demonstrated increased risk for moderate periodontitis (OR = 2.58; 95% CI = 1.28–5.18). Higher risk for moderate periodontitis was found in male with rs7762544‐AG close to NCR2 gene. The rs352140‐TT in the TLR9 gene proved to be associated with lower risk to severe periodontitis in men. The rs2521634‐AA was associated with higher percentage of interproximal probing pocket depth (P = .004).
Conclusions
This is the first evidence of validation in a Brazilian population of genetic markers of periodontitis previously investigated by GWAS and bioinformatics studies. SNPs in the NPY, IL37, and NCR2 genes were associated with susceptibility to moderate or severe periodontitis; whereas the TLR9 marker was associated with lower chance to develop severe periodontitis. Those SNPs had sex‐ and smoking‐habit‐specific effects on periodontitis; reinforcing the genetic profile predisposing to periodontitis.
Epigenetic factors are heritable genome modifications that potentially impact gene transcription, contributing to disease states. Epigenetic marks play an important role in chronic inflammatory ...conditions, as observed in periodontal diseases, by allowing microbial persistence or by permitting microbial insult to play a role in the so‐called ‘hit‐and‐run’ infectious mechanism, leading to lasting pathogen interference with the host genome. Epigenetics also affects the health sciences by providing a dynamic mechanistic framework to explain the way in which environmental and behavioral factors interact with the genome to alter disease risk. In this article we review current knowledge of epigenome regulation in light of the multifactorial nature of periodontal diseases. We discuss epigenetic tagging in identified genes, and consider the potential implications of epigenetic changes on host–microbiome dynamics in chronic inflammatory states and in response to environmental stressors. The most recent advances in genomic technologies have placed us in a position to analyze interaction effects (eg, between periodontal disease and type 2 diabetes mellitus), which can be investigated through epigenome‐wide association analysis. Finally, because of the individualized traits of epigenetic biomarkers, pharmacoepigenomic perspectives are also considered as potentially novel therapeutic approaches for improving periodontal disease status.
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