Difference in apolipoprotein E genotype distribution between dentate and edentulous elderly patients with Alzheimer disease

Association between dementia and tooth loss has been shown although the nature of that association is not clear. It has also been shown that risk of dementia was increased in apolipoprotein E4 allele carriers. The objective of this study was to determine the frequency of APOE alleles and their association with the dental status in elderly demented patients. Dental status of 67 patients with dementia was recorded. DNA was isolated from buccal swabs and genotyping was done by PCR-RFLP. The majority of participants had E3/E4 genotype (55.2%) and these heterozygotes were significantly more frequent than any other genotype (p lt 0.001). There was no significant association between dental status and genotype. However, partial edentulousness with very few teeth in both jaws (1-9 teeth) was significantly more frequent among demented patients with E3/E4 genotype (p=0.021). Patients with Alzheimer disease most frequently had E3/E4 genotype and had very few or no teeth

Methylation of tumour suppressor genes in benign and malignant salivary gland tumours: a systematic review and meta-analysis

The aim of the present systematic review was to critically analyse the relationship between tumour suppressor genes (TSGs) promoter methylation, a potent mechanism of gene silencing, and the development of salivary gland tumours, as well as the possible effect on clinical/histological characteristics. Review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (registration ID CRD42020218511). A comprehensive search of Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials was performed utilizing relevant key terms, supplemented by a search of grey literature. Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used for the quality assessment of included studies. Sixteen cross-sectional and 12 case-control studies were included in the review, predominantly dealing with methylation in TSGs related to DNA repair, cell cycle, and cell growth regulation and differentiation. Quantitative synthesis could be performed on P16 (inhibitor of cyclin-dependent kinase 4a), RASSF1A (Ras association domain family 1 isoform A) and MGMT (O6-methylguanine DNA methyltransferase) genes only. It showed that P16 and RASSF1A genes were more frequently methylated in salivary gland tumours compared to controls (P = .0002 and P < .0001, respectively), while no significant difference was observed for MGMT. Additionally, P16 did not appear to be related to malignant transformation of pleomorphic adenomas (P = .330). In conclusion, TSG methylation is involved in salivary gland tumour pathogenesis and several genes might play a considerable role. Further studies are needed for a better understanding of complex epigenetic deregulation during salivary gland tumour development and progression

Association of TNF-R2 (676T>G) single nucleotide polymorphism with head and neck cancer risk in the Serbian population

Tumor necrosis factor (TNF) which exerts its effects through two different receptors known as TNF-R1 and TNF-R2, is a major proinflammatory cytokine involved in the pathogenesis of different types of tumors. We have investigated whether polymorphisms in TNF-alpha (-308G&gt;A), TNF receptor 1 (36A&gt;G) and TNF receptor 2 (676T&gt;G) genes modulate the susceptibility for oral squamous cell carcinomas (OSCCs) and basal cell carcinomas (BCCs) of the skin, two frequent types of head and neck cancers. Genotyping was done on 50 OSCC patients, 50 BCC patients and 60 healthy individuals, using PCR/RFLP. A significant difference in genotype and allele frequencies was found between patients and controls for the TNF-R2 polymorphism, in both OSCC and BCC. There was no statistically significant difference between patients and controls for TNF-alpha and TNF-R1 polymorphisms. Carriers of G allele had an approximately 2.5- and 5-fold higher risk for OSCC and BCC, respectively, in the Serbian population

Involvement of the Notch signaling system in alveolar bone resorption

The Notch pathway is an evolutionarily preserved signaling pathway involved in a variety of vital cell functions. Additionally, it is one of the key regulators of inflammation, and controls the differentiation and function of different cells. Moreover, it was found to be involved in skeletal development and bone remodeling process. This review provides an overview of the involvement of the Notch signaling pathway in the pathogenesis of alveolar bone resorption in different forms of pathological conditions such as apical periodontitis, periodontal disease, and peri-implantitis. In vitro and in vivo evidence have confirmed the involvement of Notch signaling in alveolar bone homeostasis. Nonetheless, Notch signaling system, along with complex network of different biomolecules are involved in pathological process of bone resorption in apical periodontitis, periodontitis, and peri-implantitis. In this regard, there is a substantial interest to control the activity of this pathway in the treatment of disorders associated with its dysregulation. This review provides knowledge on Notch signaling and outlines its functions in alveolar bone homeostasis and alveolar bone resorption. Further investigations are needed to determine whether inhibition of the Notch signaling pathways might be beneficial and safe as a novel approach in the treatment of these pathological conditions

Clinical and microbiological effects of the initial periodontal therapy

Introduction. Periodontitis is a destructive inflammatory disease of the tooth-supporting tissues, primarily caused by Gram-negative microorganisms. Thus, the primary objective of cause-related initial periodontal therapy is disruption and removal of the subgingival biofilm. Objective. The aim of this study was to evaluate the clinical and microbiological effects of the initial therapy in patients diagnosed with chronic periodontitis. Methods. Forty patients with chronic periodontitis were included in the study. As a part of the clinical assessment undertaken prior to the initial therapy, as well as one month and three months post-therapy, plaque index, gingival index, papilla bleeding index, probing pocket depth and clinical attachment level were recorded. Microbiological testing was performed prior to the initial therapy and three months after therapy. Polymerase chain reaction assays were used to determine the presence of Porphyromonas gingivalis, Tannerella forsythensis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans. Results. All clinical parameters were significantly reduced after therapy. The prevalence of Aggregatibacter actinomycetemcomitans was reduced by 22.5%, which was a statistically significant decrease compared to the baseline. The prevalence of Porphyromonas gingivalis, Tannerella forsythensis and Prevotella intermedia tended to decrease after therapy; however, the difference did not reach statistical significance. Conclusion. The results of the present study demonstrated the beneficial effects of the initial periodontal therapy on both the clinical and microbiological parameters. [Projekat Ministarstva nauke Republike Srbije, br. 175075

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

Background: The interaction between heredity and different environmental factors in the modification of apical periodontitis (AP) susceptibility and prediction of its progression remain poorly elucidated. Objectives: 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. Methods: 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. Results: 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. Discussion: 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. Conclusions: 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

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma

The aim of this study was to assess TERT-CLPTM1L single-nucleotide polymorphisms (SNPs) (rs402710 C/T in the CLPTM1L gene; rs2736100 A/C and rs2736098 G/A in the TERT gene) as risk factors for development of oral squamous cell carcinoma (OSCC), and to investigate the relationship between the analyzed polymorphisms, relative telomere length (RTL), telomerase expression and clinicopathologic characteristics of OSCC in a Serbian population. Paraffin-embedded tumor samples and buccal swabs from cancer-free controls were genotyped using PCR-RFLP, while tumor RTL values and telomerase expression were estimated by real-time PCR and immunohistochemistry, respectively. CLPTM1L rs402710 and TERT rs2736100 polymorphisms were associated with a significantly increased risk of OSCC, and TERT rs2736098 with a significantly decreased risk. No significant association was found between TERT-CLPTM1L polymorphisms, tumor RTL values, telomerase expression, and clinicopathologic features, although a trend towards longer telomeres was evident in telomerase-positive samples and less advanced tumors. Kaplan-Meier survival analysis showed that patients with longer telomeres in their tumors had significantly better overall survival than patients with shorter telomeres. Our research seems to provide strong evidence for an association between CLPTMIL rs402710C/T and TERT rs2736100A/C SNPs and the risk of OSSC, and suggests that higher tumor RTL values and positive hTERT expression may be applicable as early prognostic markers

P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population

Objective. To investigate the prevalence of p16(INK4) (a), p14(ARF), tumor protein p53 (TP53), and human telomerase reverse transcriptase (hTERT) promoter hypermethylation in mucoepidermoid carcinomas (MECs) and search for a possible association between methylation status and clinicopathological parameters. Study design. DNA extracted from 35 formalin-fixed and paraffin-embedded MEC samples and 10 normal salivary gland (NSG) tissue samples was analyzed for the presence of promoter hypermethylation using methylation-specific polymerase chain reaction testing. Results. The percentages of gene hypermethylation in MECs versus NSGs were the following: p14: 100% versus 20% (P LT .001); p16: 60% versus 20% (P = .035); hTERT: 54.3% versus 20% (P = .078); and TP53: 31.4% versus 30% (P = .981). Multiple sites were found to be methylated in 86% of MECs compared with 10% in NSGs (P LT .001). TP53 and hTERT were more often methylated in lower clinical stages (P = .033 and P = .005, respectively). Conclusions. Hypermethylation of p14 appears to be an important event in the development of mucoepidermoid carcinoma. High frequency of gene hypermethylation and high incidence of methylation at multiple sites point to the importance of epigenetic phenomena in the pathogenesis of MECs, although with modest impact on clinical parameters

High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors

Objectives: to investigate p16(INK4a) and p14(ARF) tumor suppressor gene methylation status, determine telomere length and assess the importance of these epigenetic and genetic parameters in the development of pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid salivary glands. Materials and Methods: Genomic DNA from paraffin-embedded samples of 50 pleomorphic adenomas and 10 carcinomas ex pleomorphic adenoma was subjected to methylation specific polymerase chain reaction for hypermethylation analyses and real time polymerase chain reaction for the relative telomere length calculations. Results: Promoter hypermethylation of the two genes was a very frequent event in both neoplasms between 60% and 90% of samples were hypermethylated - but without significant difference between the groups. The mean relative telomere length in the pleomorphic adenoma group was significantly increased in comparison to the control group (P = 0.00), and significantly decreased in comparison to the carcinoma group (P = 0.05). Telomeres were also longer in myxoid and cellular histological subtypes of adenomas than in the classic type (P = 0.044 and P = 0.018, respectively). Longer telomeres were more frequent in tumors with hypermethylated p14(ARF) alleles (P = 0.013). Conclusion: Promoter hypermethylations seems to be an important mechanism of p16(INK4a) and Pl4(ARF) inactivation in parotid gland tumors. Telomeric lengthening appears to be involved in the pathogenesis of both benign and malignant tumors of the parotid glands. (C) 2015 Elsevier Ltd. All rights reserved