Periodontitis Susceptibility Research Articles

Role of CD86 on granulocyte in mediating the effect of Genus Roseburia on periodontitis.

This study aimed to explore the causal link between the gut microbiota and periodontitis, and to delineate and quantify the intermediary role of immune cells, so as to provide new insights into the pathogenesis, prevention and treatment of periodontitis. We employed a two-sample Mendelian randomization (MR) approach to analyze the genetic predictors of gut microbiota composition (covering 412 gut microbiota taxa and functions) and periodontitis (involving 4,784 cases and 272,252 controls) derived from genome-wide association study (GWAS) datasets. A subsequent two-step MR analysis was conducted to evaluate the extent to which immune cell traits (encompassing 731 immune cell characteristics) mediate the influence of gut microbiota on periodontitis risk. Our analysis implicated nine gut microbiota taxa as causal factors in periodontitis susceptibility (p < 0.05). Notably, the Genus Roseburia was identified as exerting a protective effect against periodontitis, partially mediated through the upregulation of CD86 expression on granulocytes, with an 8.15% mediation effect observed. Our findings establish a causal relationship between the gut microbiota and periodontitis, highlighting the protective role of Roseburia against this condition. A notable proportion of this protective effect is mediated via the upregulation of CD86 on granulocytes. It can provide new ideas for the pathogenesis, prevention and treatment for periodontitis through exploring the causal link between the gut microbiota and periodontitis, and describing and quantifying the intermediary role of immune cells.

Marginal Bone Level Changes Evaluation of Long-term Functional Dental Implants with the Implant Disease Risk Assessment Diagram: A 2 to 6 Years Follow-up Retrospective Study.

Purpose: This study aimed to evaluate the relationship between risk profile assessments of dental implants that have been in function for at least two-year and peri-implant marginal bone loss during the follow-up period using the Implant Disease Risk Assessment Diagram. Material and Methods: A total of 70 patients and 170 implants who had been functionally loaded for at least two years and who attended follow-up sessions were included in the study. Full-mouth plaque index (PI), gingival index (GI), probing depth (PD), bleeding on probing, clinical attachment level (CAL), and peri-implant modified plaque index, modified bleeding index, PD, keratinized mucosal width (KMW), CAL and GR were recorded. According to the IDRA risk diagram, participants and dental implants were divided into low, moderate, and high-risk groups. Marginal bone level (MBL) was measured on periapical radiographs obtained at functional loading (T0) and at the last follow-up session (T1), and mesial and distal marginal bone level changes (ΔMBL) were calculated as T1-T0. Results: A statistically significant correlation was found between the periodontitis history and periodontitis susceptibility and IDRA classification at the patient-level. Full-mouth GI, PD, and BOP were found to be statistically higher in the high-risk IDRA group. No statistically significant result was found between the mesial and distal ΔMBL between the IDRA risk groups.Conclusions: In this study, IDRA risk level increased especially by periodontitis susceptibility and periodontitis history, but no significant difference was found between risk groups in terms of ΔMBL.

Exploring Putative Causal Associations between Diet and Periodontal Disease Susceptibility.

Dietary factors may play an important role in periodontal health. However, current evidence from observational studies remains inconclusive. This study aimed to investigate the causal relationships between dietary exposures and periodontal disease risks using Mendelian randomization analysis. Large-scale genome-wide association study summary statistics for 20 dietary factors were obtained from the MRC-IEU consortium. Multivariable and univariable 2-sample Mendelian randomization analyses were performed to assess the causal effects of each dietary exposure on 6 periodontal outcomes, including gingivitis and periodontitis. Genetically predicted higher dried fruit intake was significantly associated with reduced risks of acute gingivitis (odds ratio [OR]: 0.02; 95% confidence interval [CI]: 0.00-0.42; P = 0.01) and bleeding gums (OR: 0.96; 95% CI: 0.93-0.99; P = 0.01). Higher fresh fruit and water intake showed protective effects against chronic gingivitis (OR: 0.18; 95% CI: 0.04-0.91; P = 0.04 and OR: 0.15; 95% CI: 0.04-0.53; P = 0.00) and bleeding gums (OR: 0.95; 95% CI: 0.92-0.981; P = 0.00 and OR: 0.98; 95% CI: 0.96-0.99; P = 0.02). Alcohol intake frequency and processed meat intake were risk factors for bleeding gums (OR: 1.01; 95% CI: 1.00-1.02; P = 0.01 and OR: 1.05; 95% CI: 1.01-1.08; P = 0.00) and painful gums (OR: 1.01; 95% CI: 1.00-1.01; P = 0.00 and OR: 1.02; 95% CI: 1.01-1.03; P = 0.00). Most of the causal relationships between genetic predisposition to the specified dietary factors and periodontal diseases remained statistically significant (P < 0.05) after adjusting for genetic risks associated with dentures, smoking, and type 2 diabetes in multivariable Mendelian randomization models. The findings suggest potential protective effects of higher fruit and water intake against gingivitis and other periodontal problems, while alcohol and processed meat intake may increase the risks of periodontal disease. Our study provides preliminary causal evidence on the effects of diet on periodontal health and could inform prevention strategies targeting dietary habits to improve oral health. This study suggests that fruit and water intake may protect against periodontal disease, while alcohol and processed meats increase risk, informing dietary guidelines to improve oral health.

Exploring the role of epigenetics in periodontal disease progression: A narrative review

Periodontal disease remains a significant global health concern, characterized by chronic inflammation and destruction of the tooth-supporting structures. While microbial dysbiosis is a well-established factor in its pathogenesis, emerging evidence suggests that epigenetic modifications play a crucial role in the initiation and progression of periodontal disease. This narrative review aims to synthesize current knowledge on the intricate interplay between epigenetics and periodontal disease progression. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, regulate gene expression patterns without altering the underlying DNA sequence. Dysregulation of these mechanisms can disrupt inflammatory and immune responses, exacerbating periodontal tissue damage. Various studies have highlighted specific epigenetic alterations associated with periodontal disease, such as aberrant DNA methylation patterns in promoter regions of key inflammatory genes and dysregulated microRNA expression profiles implicated in tissue remodeling processes. Moreover, environmental factors, such as smoking, diet, and stress, can modulate epigenetic signatures, further influencing periodontal disease susceptibility and severity. Understanding the epigenetic landscape of periodontal disease offers new avenues for therapeutic interventions and personalized treatment strategies. Targeting epigenetic regulators may provide innovative approaches to mitigate inflammation, promote tissue regeneration, and ultimately improve clinical outcomes in patients with periodontal disease. In conclusion, epigenetics plays a significant role in periodontal disease progression by regulating inflammatory and tissue remodeling pathways. Future research should continue to elucidate the complex epigenetic mechanisms underlying periodontal disease pathogenesis, paving the way for novel therapeutic interventions and personalized management strategies.

Estimating Periodontitis Susceptibility Cases for Epidemiological Studies with Multiple Imputation.

Our proposed estimate of periodontitis susceptibility cases addresses the issue of missing teeth, offering an innovative solution through a generative missing data imputation model. The implications of our findings extend to fostering more robust investigations into the relationships between periodontal health and systemic diseases, thereby offering valuable insights to clinicians for informed decision-making. Moreover, the study's capacity to shape clinical practices and interventions in public health will further fortify health policy strategies.

Glutathione S-transferase M1, T1, and P1 polymorphisms and periodontitis in a Caucasian population: a case-control study

BackgroundGlutathione S-transferases (GSTs) play important roles in protecting cells against oxidative stress and toxic chemicals. This study aimed to investigate the distribution of GSTM1, GSTT1, and GSTP1 variants and their roles in periodontitis susceptibility in a Caucasian population.MethodsWe analyzed 406 participants, including 204 healthy controls and 203 periodontitis patients. A multiplex polymerase chain reaction (PCR) approach was used to analyze GSTM1 and GSTT1 loci. GSTP1 variants were detected by PCR-haplotyping method in a subgroup of participants (N = 350). Chi-square or Fisher´s exact tests were used to compare genotypic and allelic differences. The Bonferroni method was applied to correct for multiple comparisons (pcorr).ResultsThe GSTM1 genotype distribution did not differ significantly between controls and periodontitis patients (p = 0.44). Additionally, the wild/null genotypes of GSTT1, Ile105Val and Ala114Val frequencies of GSTP1 were not significantly different between the two groups after correction for multiple comparisons (p = 0.05, p = 0.55, p = 0.02, pcorr>0.05, respectively). The GSTM1 and GSTP1 Ile105Val gene variants were similarly distributed between non-smokers and smokers in both groups (p = 0.38, p = 0.20, and p = 0.14, p = 0.35, respectively). However, the wild genotype of the GSTT1 and Ala114Ala variant of the GSTP1 genes were present more frequently in non-smoking periodontitis patients than in non-smoking controls (p = 0.03, pcorr>0.05, and p = 0.009, pcorr>0.05, respectively) although their frequencies did not differ between smoking periodontitis patients and smoking controls (p = 0.23, p = 0.68, respectively).ConclusionsThis study in a Czech Caucasian population did not confirm a highly significant association between GST gene variants and susceptibility to periodontitis, as previously reported by Arshad and colleagues in Pakistanis. However, a weak relationship between GSTT1 and GSTP1 rs1138272 polymorphisms and periodontitis in non-smokers was observed.

The Complex Interplay between C-reactive Protein and Periodontal Health: A Narrative Review

ABSTRACT Aim: The aim of this review is to comprehensively explore and elucidate the intricate relationship between C-reactive protein (CRP) levels and periodontal health. It involves an examination of the existing literature to understand the role of CRP as a biomarker and potential mediator in the pathogenesis, progression, and management of periodontal disease. Material and Methods: A literature search was conducted between January 2010 and December 2023, in PubMed/MEDLINE, Google Scholar, and Scopus databases, using keywords such as “acute phase reactants,” “C-reactive protein,” “cardiovascular disease,” and “periodontal disease” combined by Boolean operators. Employing a multistep screening process, which included literature search, evaluation of article titles and abstracts, and full-text reading, we considered studies that met the inclusion/exclusion criteria for the review. Results: Twenty-two articles meeting the inclusion and exclusion criteria were selected for analysis, focusing on the association between CRP and periodontal diseases. The findings consistently demonstrated a positive correlation, implying a potential nexus between periodontal inflammation and systemic inflammatory processes as evidenced by elevated CRP levels. Conclusion: This review article aims to provide a comprehensive overview of the complex relationship between CRP and periodontal health, also shedding light on novel insights that have been uncovered in recent research. It discusses the role of CRP as an acute-phase reactant, which explores the role of CRP in modulating inflammatory pathways, endothelial dysfunction, and oxidative stress within the periodontal tissues. Furthermore, the impact of genetic variations in the CRP gene on periodontal disease susceptibility and severity is discussed. It explores the potential of CRP as a diagnostic and prognostic marker for periodontal disease and its role in assessing treatment outcomes and predicting systemic health risks associated with periodontitis and open avenues for targeted therapeutic strategies and personalized approaches to periodontal management.

Association between polymorphisms of anti-inflammatory gene alleles and periodontitis risk in a Chinese Han population.

Cytokines that mediate the immune responses are important in the pathogenesis of periodontitis. The genetic polymorphisms of IL-10, TNFAIP3 (A20), and NF-κB1 (p105/p50) and their association with the risk of periodontitis were investigated. Venous blood from 102 clinical periodontal healthy participants and 100 patients with periodontitis was collected to genotype the IL-10 (rs1800872), A20 (rs2230926, rs5029937, rs6927127), and NF-κB1 (rs28362491) SNP loci by Sanger technology. Univariable and multivariable logic regression and path analysis model was used to analyze the genotypes and alleles. Single-gene mutations in the A20 (rs2230926, rs5029937, rs6927127) and IL-10 (rs1800872) genes were not associated with the risk of periodontitis. NF-κΒ1 (rs28362491) gene influenced periodontitis susceptibility by affecting CAL. The combined effect of A20 and IL-10 was related to the risk of periodontitis (ORa = 0.123-0.151). One site mutated in the A20 (rs2230926, rs5029937, rs6927127) gene or IL-10 (rs1800872) gene reduced the risk of periodontitis. Single gene polymorphisms in A20 and IL-10 genes were not associated with the risk of periodontitis. NF-κB1 gene polymorphism indirectly affects susceptibility to periodontitis. The combined effect of anti-inflammatory gene polymorphisms (A20 and IL-10) correlated with the decreased risk of periodontitis. This study helps to explore the potential mechanisms underlying the role of anti-inflammatory genes in the progression of periodontal disease and provides a basis for the selection and development of appropriate periodontal treatment strategies based on the genetic profile of the patient.

Genetic Control of GCF Exudation: Innate Immunity Genes and Periodontitis Susceptibility.

Chronic periodontitis is a bacterial infection associated with dentally adherent biofilm (plaque) accumulation and age-related comorbidities. The disease begins as an inflammatory exudate from gingival margins, gingival crevicular fluid (GCF) in response to biofilm lysine. After a week of experimental gingivitis (no oral hygiene), biofilm lysine concentration was linearly related to biofilm accumulation (plaque index) but to GCF as an arch-shaped double curve which separated 9 strong from 6 weak GCF responders (hosts). Host DNA was examined for single nucleotide polymorphisms (SNPs) of alleles reported in 7 periodontitis-associated genes. Across all 15 hosts, an adenine SNP (A) at IL1B-511 (rs16944), was significant for strong GCF (Fisher's exact test, p < 0.05), and a thymidine SNP (T) at IL1B+3954 (rs1143634) for weak GCF provided 2 hosts possessing IL6-1363(T), rs2069827, were included. The phenotype of IL1B+3954(T) was converted from weak to strong in one host, and of the non-T allele from strong to weak in the other (specific epistasis, Fisher's exact test, p < 0.01). Together with homozygous alternate or reference SNPs at IL10-1082 or CD14-260 in 4 hosts, all hosts were identified as strong or weak GCF responders. The GCF response is therefore a strong or weak genetic trait that indicates strong or weak innate immunity in EG and controllable or uncontrollable periodontal disease, dental implant survival and late-life comorbidities.

Diabetes mellitus promotes susceptibility to periodontitis-novel insight into the molecular mechanisms.

Diabetes mellitus is a main risk factor for periodontitis, but until now, the underlying molecular mechanisms remain unclear. Diabetes can increase the pathogenicity of the periodontal microbiota and the inflammatory/host immune response of the periodontium. Hyperglycemia induces reactive oxygen species (ROS) production and enhances oxidative stress (OS), exacerbating periodontal tissue destruction. Furthermore, the alveolar bone resorption damage and the epigenetic changes in periodontal tissue induced by diabetes may also contribute to periodontitis. We will review the latest clinical data on the evidence of diabetes promoting the susceptibility of periodontitis from epidemiological, molecular mechanistic, and potential therapeutic targets and discuss the possible molecular mechanistic targets, focusing in particular on novel data on inflammatory/host immune response and OS. Understanding the intertwined pathogenesis of diabetes mellitus and periodontitis can explain the cross-interference between endocrine metabolic and inflammatory diseases better, provide a theoretical basis for new systemic holistic treatment, and promote interprofessional collaboration between endocrine physicians and dentists.

Roles of Pyroptosis-Related Genes in the Diagnosis and Subtype Classification of Periodontitis.

Pyroptosis is widely involved in many diseases, including periodontitis. Nonetheless, the functions of pyroptosis-related genes (PRGs) in periodontitis are still not fully elucidated. Therefore, we aimed to investigate the role of PRGs in periodontitis. Three datasets (GSE10334, GSE16134, and GSE173078) from the Gene Expression Omnibus (GEO) were selected to analyze the differences in expression values of the PRGs between nonperiodontitis and periodontitis tissue samples using difference analysis. Following this, five hub PRGs (charged multivesicular body protein 2B, granzyme B, Z-DNA-binding protein 1, interleukin-1β, and interferon regulatory factor 1) predicting periodontitis susceptibility were screened by establishing a random forest model, and a predictive nomogram model was constructed on the basis of these genes. Decision curve analysis suggested that the PRG-based predictive nomogram model could provide clinical benefits to patients. Three distinct PRG patterns (cluster A, cluster B, and cluster C) in the periodontitis samples were revealed according to the 48 significant PRGs, and the difference in the immune cell infiltration among the three patterns was explored. We observed that all infiltrating immune cells, except type 2 T helper cells, differ significantly among the three patterns. To quantify the PRG patterns, the PRG score was calculated by principal component analysis. According to the results, cluster B had the highest PRG score, followed by cluster A and cluster C. In conclusion, PRGs significantly contribute to the development of periodontitis. Our study of PRG patterns might open up a new avenue to guide individualized treatment plans for patients with periodontitis.

Susceptibility of periodontitis and its impact on patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) and periodontitis are chronic, progressive, inflammatory diseases with similarly complex pathogeneses that include dysbiotic microbiota and dysregulated immune-inflammatory responses, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the emerging evidence dealing with the susceptibility of periodontal disease and its impacts on patients with IBD by explaining the risk factors, possible pathogenic interactions, and disease activity by reviewing recent literature from open-source journals on the same topic. There seems to be an increased prevalence of periodontitis in patients with IBD when compared to healthy controls, which was more pronounced in ulcerative colitis (UC) than Crohn’s disease (CD). In addition, both greater severity and extent of periodontitis have been found in IBD patients when compared to healthy controls. Age, gender, lifestyle or environmental factors, and smoking history were the associated risk factors. In conclusion, the findings suggest that patients with IBD be kept under close surveillance to prevent periodontitis and/or mitigate its progression. Oral health education and effective treatment are required for IBD patients. However, we still need more data derived from human studies to confirm the results. Thus, mechanistic studies are warranted to clarify this possible bidirectional association.

Bromelain inhibits the inflammation and senescence effect in diabetic periodontitis: A preliminary in vitro study

Background/purposeDiabetes mellitus (DM) is a chronic metabolic disorder that affects millions of people worldwide. A growing evidence suggests that hyperglycemia in DM causes a pre-aging and pro-inflammatory condition known as inflammaging, which increases periodontitis susceptibility. Bromelain has been demonstrated to have anti-inflammatory and anti-aging properties in variety of tissues, but its effects on diabetic periodontitis remain unclear. Thus, the aim of this study is to investigate the its Bromelain's impact in diabetic periodontitis in terms of inflammation and senescence activity. Materials and methodsWe assessed the wound healing capacity, production of pro-inflammatory cytokines Interleukin (IL)-6 and IL-8 and senescence marker p16 in human gingival fibroblasts (HGFs) in response to Advanced glycation end-products (AGEs) stimulant, with or without Bromelain treatment. The expression of p65, p-ERK, and p-p38 were also examined to elucidate whether Bromelain's anti-inflammaging activity is mediated through NF-κB and MAPK/ERK signaling pathway. ResultsBromelain concentrations ranging from 2.5 to 20 g/mL had no adverse effect on HGF cell proliferation. Bromelain improved wound healing in HGFs with AGEs stimulation. In addition, Bromelain suppressed the production of pro-inflammatory cytokines IL-6 and IL-8 in HGFs elicited by AGEs. Meanwhile, Bromelain treatment also inhibited the senescence activity and expression of p16 in AGEs-stimulated HGFs. Western blot analysis indicated that the upregulation of p-ERK, p-p38 and p65 induced by AGEs were inhibited by Bromelain in HGFs. ConclusionThese data suggest that excessive AGEs in the gingiva may lead to the accumulation of pro-inflammatory cytokines and marked senescence activity. Bromelain application may be helpful in enhancing wound healing by suppressing inflammaging via downregulation of NF-κB and MAPK/ERK signaling pathways in DM individuals with periodontal disease.

Expression of periodontitis susceptibility genes in human gingiva using single-cell RNA sequencing.

Single-cell transcriptomics was used to determine the possible cell-type specificity of periodontitis susceptibility genes. The last decade has witnessed remarkable advances in the field of human genomics. Despite many advances, the genetic factors associated with or contributing to the periodontitis pathogenesis have only been identified to a limited extent and are often poorly validated. Confirming whether a given single nucleotide polymorphism has an association with periodontitis requires a robust mechanistic explanation on the functional consequences of a given genetic variant. We globally assessed the expression of 26 disease-associated genes identified by GWAS within the gingival mucosa. A total of 12 411 cells from 4 different donors were analysed. Differentially expressed genes were analysed using Seurat, a non-parametric Wilcoxon rank sum test. The minimum threshold for significance was defined as p < .05. This exploration at a cellular-level suggests diverse populations contributing to disease pathogenesis, with macrophages expressing a higher number of the analysed disease-associated genes. IL1B, PTGS2, FCGR2A, IL10 and IL1A specifically showed a more restricted expression in the myeloid lineages. This short report combines human genetics and single-cell genomics to better understand periodontitis by mapping variants to predict their cells of action and putative functions. These findings seem to suggest that innate cell dysfunction is linked to disease susceptibility.

Case-only design identifies interactions of genetic risk variants at SIGLEC5 and PLG with the lncRNA CTD-2353F22.1 implying the importance of periodontal wound healing for disease aetiology.

The basis of phenotypic variation of periodontitis is genetic variability. Disease relevant effects of individual risk alleles are considered to result from genetic interactions. We investigated gene × gene (G×G) interactions of suggestive periodontitis susceptibility alleles. We used the case-only design and investigated single-nucleotide polymorphism (SNPs) that showed associations in our recent genome-wide association study (GWAS) and GWAS meta-analysis with p < 5 × 10-6 . CRISPR-dCas9 gene activation followed by RNA-sequencing and gene-set enrichment analyses elucidated differentially expressed genes and gene networks. With the databases of SNPInspector and Transfac professional, luciferase reporter gene assays and antibody electrophoretic mobility shift experiments, we analysed allele-specific effects on transcription factor binding. SNPs at the genes sialic acid binding Ig-like lectin 5 (SIGLEC5) and plasminogen (PLG) showed G×G interactions with rs1122900 at the long non-coding RNA (lncRNA) CTD-2353F22. Associated chromatin cis-activated CTD-2353F22.1 6.5-fold (p=.003), indicating CTD-2353F22.1 as target gene of this interaction. CTD-2353F22.1 regulated GADD45A (padj < 4.9 × 10-11 , log2 fold change (FC)=-0.55), THBS1, SERPINE1 and Tissue Factor F3 (padj < 5 × 10-7 , log2 FC ≥ -0.35) and the gene set "angiogenesis" (area under the curve=0.71, padj =8.2 × 10-5 ). rs1122900 effect C-allele decreased reporter gene activity (5.5-fold, p=.0003) and PRDM14 binding (76%). CTD-2353F22.1 mediates interaction of SIGLEC5 and PLG, together with genes that function in periodontal wound healing.

The Action of Gene Polymorphism in the pathogenesis of periodontal diseases: A Narrative Review

Presently, it is known that pathogenic bacteria are the key factors for the initiation of periodontal disease, but the host response and the severity of clinical expression are largely determined by genetic susceptibility and environmental factors. There is evidence that the individual response to the environment and variations in the immune response in periodontitis are associated with genetic factors. The gene polymorphisms like interleukin-1 beta (IL-1b), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-a) genes and their factors that determine the production of various cytokines which play an important role in the pathophysiology of inflammation and periodontal diseases. A sequel of this realization is that if the genetic basis of periodontal disease susceptibility can be understood, such information may have diagnostic and therapeutic value. This review focus to upgrade the general practitioners and periodontist about various genetic polymorphisms associated with periodontal diseases to aid in a better approach to the condition in the future.

Epigenetics in susceptibility, progression, and diagnosis of periodontitis.

Periodontitis is characterized by irreversible destruction of periodontal tissue. At present, the accepted etiology of periodontitis is based on a three-factor theory including pathogenic bacteria, host factors, and acquired factors. Periodontitis development usually takes a decade or longer and is therefore called chronic periodontitis (CP). To search for genetic factors associated with CP, several genome-wide association study (GWAS) analyses were conducted; however, polymorphisms associated with CP have not been identified. Epigenetics, on the other hand, involves acquired transcriptional regulatory mechanisms due to reversibly altered chromatin accessibility. Epigenetic status is a condition specific to each tissue and cell, mostly determined by the responses of host cells to stimulations by local factors, like bacterial inflammation, and systemic factors such as nutrition status, metabolic diseases, and health conditions. Significantly, epigenetic status has been linked with the onset and progression of several acquired diseases. Thus, epigenetic factors in periodontal tissues are attractive targets for periodontitis diagnosis and treatments. In this review, we introduce accumulating evidence to reveal the epigenetic background effects related to periodontitis caused by genetic factors, systemic diseases, and local environmental factors, such as smoking, and clarify the underlying mechanisms by which epigenetic alteration influences the susceptibility of periodontitis.

Gingival crevicular fluid from pregnant women impairs trophoblast cell function and trophoblast‐neutrophil interaction

A strong association between periodontitis and higher susceptibility to pregnancy complications like preeclampsia has been reported although the mechanisms remain elusive. Trophoblast cells modulate the recruitment and functional shaping of maternal leukocytes at early stages to sustain an antiinflammatory microenvironment and fetal growth. Neutrophil activation with reactive oxygen species (ROS) release is associated with preeclampsia. Our aim was to study the effect of the gingival crevicular fluid (GCF) from pregnant women on trophoblast cell function and trophoblast-neutrophil interaction. Pregnant women at 16-20weeks of gestation (n=27) and non-pregnant women (n=8) as the control group were studied for gingivoperiodontal clinical score evaluation and GCF collection. Total bacteria and common periodontal pathogens were analyzed in GCF samples. The effect of each GCF sample was tested on first trimester trophoblast-derived cells to assess cell migration, cytokine expression and glucose uptake. Also, the effect of GCF on human peripheral neutrophil chemoattraction by trophoblast cells and ROS formation was assessed. Gingival crevicular fluid from pregnant women reduced trophoblast cell migration, increased proinflammatory marker expression and glucose uptake. A significant correlation between gingivoperiodontal score and trophoblast dysfunction was observed. Upon conditioning of trophoblast cells with GCF, only the GCF from pregnant women stimulated neutrophil chemoattraction. Similarly, GCF from pregnant but not from non-pregnant controls stimulated ROS formation in neutrophils. Gingival crevicular fluid from pregnant women is deleterious for first trimester trophoblast cell function. These effects could lead to placental homeostasis disruption underlying a pathogenic mechanism of pregnancy complications associated to periodontal disease.

Single nucleotide polymorphisms as a predisposing factor for the development of apical periodontitis-An umbrella review.

The interaction between heredity and different environmental factors in the modification of apical periodontitis (AP) susceptibility and prediction of its progression remain poorly elucidated. This umbrella review aimed to (i) analyse the available relevant systematic reviews in an attempt to determine the association between genotype and allelic distribution of different single-nucleotide polymorphisms (SNPs) and the development of AP, (ii) report deficiencies and gaps in knowledge in this area and (iii) present recommendations to conduct future clinical studies and systematic reviews. A literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed and Cochrane Database of Systematic Reviews, from inception to October 2021, with no language restrictions, including a grey literature search. Systematic reviews with/without meta-analysis evaluating genotype and allelic distribution of different SNPs between adult patients with/ without AP were included. All other type of studies were excluded. The methodological quality was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR)-2 tool. Two independent reviewers were involved in study selection, data extraction and appraising the included reviews; disagreements were resolved by a third reviewer. The current study includes five systematic reviews. Three reviews performed meta-analysis. Three reviews were graded by AMSTAR 2 as 'critically low' quality, whereas the other two were graded as 'low' and 'moderate' quality. Two reviews indicated that carriers of specific genotypes and alleles of tumour necrosis factor-alpha (TNF-α) -308 G > A and interleukin 1-beta (IL-1β) + 3954 C/T gene polymorphisms are more susceptible to an acute and persistent form of AP. However, high heterogeneity was observed. The statistical heterogeneity within included systematic reviews was a consequence of clinical and methodological diversity amongst primary studies. Although some of the included reviews suggested that carriers of specific genotype and/or allele of TNF-α -308 G > A and IL-1β + 3954 C/T SNPs are more susceptible to AP, their conclusions should be interpreted with caution. No candidate genes could be identified as a definitive genetic risk or protective factor for the development and progression of AP, and further high-quality genome-wide association studies are warranted.

Effect of tumor necrosis factor alpha (TNF-α) -308 and -1031 gene polymorphisms on periodontitis among Saudi subjects

ObjectivesPeriodontitis is an infectious disorder that leads to irreversible loss of the surrounding attachment and bone destruction. Genetic polymorphism of cytokines has been suggested to play a role in periodontitis. This case-control study aimed to investigate the relationship between periodontitis and two single nucleotide polymorphisms (SNPs): rs1800629 (-308 G/A) and rs1799964 (-1031 T/C), in the TNF-α gene promoter area. Materials and methodsPeripheral blood was used to prepare genomic DNA from 60 subjects with stage II to stage III periodontitis, as along with 65 control subjects. Polymerase chain reaction and restriction endonuclease digestion were used to genotype TNF-α SNPs. ResultsThe distribution of both genotypes and alleles of TNF-α (-308 G/A) polymorphism did not vary between periodontitis subjects and the controls (P > 0.05). However, the CT genotype and C allele of the TNF-α (-1031 T/C) polymorphism were observed more frequently in the periodontitis subjects than in the controls, while the TT genotype and the T allele were more predominant in the control subjects than in the periodontitis patients (OR: 3.149; 95% CI: 1.494–6.639; P = 0.002 and OR: 2.933; 95% CI: 1.413–6.090; P = 0.003, sequentially). ConclusionThe TNF-α (-308 G/A) polymorphism potentially has no correlation with periodontitis susceptibility, whereas the TNF-α (-1031) CT genotype and C allele might be related to periodontitis among Saudi subjects.