Potential role of TP63 in apical periodontitis development

Abstract

Aim To investigate the expression of TP63 in apical periodontitis (AP) tissues and the association of single nucleotide polymorphisms (SNPs) in the TP63 gene with AP using a case‐control dataset. Methodology Expression of TP63 in human AP lesions (apical abscess, radicular cyst, periapical granuloma) was evaluated using immunohistochemistry. A case‐control association study was performed to assess the association of TP63 polymorphisms in individuals having AP with or without associated pain. Cases were defined as subjects with deep caries and AP (n = 151) and subjects with symptomatic apical periodontitis or acute apical abscess (n = 124). Subjects without AP (n = 169) and asymptomatic (n = 196) were used as controls, respectively. Saliva samples were collected as source of genomic DNA. Twelve SNPs in the TP63 gene were selected for genotyping using Taqman chemistry in real‐time PCR. Data analysis was performed using PLINK software. The Bonferroni method was applied to correct for multiple testing; α ≤ 0.004 indicates significant differences between groups. Results TP63 expression was evident in apical abscesses and radicular cysts, while weaker expression was observed in periapical granulomas. Positive expression was observed in mononuclear cells in the granulation tissues of all AP lesions. Regarding the presence of AP, a trend for allelic association was observed for rs16864812 and rs9810322 (P = 0.04) and rs9810322 genotypes were also nominally associated with AP under a dominant model (P = 0.04). When considering the presence of periapical pain, a trend for allelic and genotypic association was observed for rs10155037 (P = 0.03). Haplotypes were also associated with AP and periapical pain (P ≤ 0.05). Conclusions Apical periodontitis is a complex multifactorial condition and it is likely that multiple genes and environmental effects may influence its susceptibility, progression or both. TP63 variants may play a role in AP pathogenesis and susceptibility, individually or interactively with other genes. Additional studies in other populations and functional studies are needed to improve understanding of the role of TP63 in AP.

P63 and Ki-67 expression in radicular cyst

“…Several studies have investigated P63 expression in RC. 7 , 8 , 9 , 10 , 11 Intriguingly, our group have confirmed such correlation between P63 and Ki-67 expressions in dentigerous cyst and odontogenic keratocyst. 12 The aim of this study was to identify the expression of P63 and its relation to odontogenic epithelial cell proliferation, severity of the inflammatory infiltrate and size of RCs.…”

“…Several previous studies investigated P63 expression in RC. 7 , 8 , 9 , 10 , 11 Positivity rates were 85.7%, 7 91.43, 9 and 100% 8 , 10 , 11 in the odontogenic epithelium of the studied cysts. It is clear that P63 expression in the present study is in comparison with the available findings.…”

“… 7 , 8 , 9 Other studies found a higher positivity rate of P63 in the odontogenic epithelium of RC than that of dentigerous cyst 8 and apical granuloma. 11 Contrary, no significant difference was observed in P63 expression among RC, odontogenic keratocyst, and dentigerous cyst. 10 The high expression of ΔNp63 in RC samples could help in the existence and persistence of these intra bony lesions.…”

Comparative Metabolomics Reveals the Microenvironment of Common T-Helper Cells and Differential Immune Cells Linked to Unique Periapical Lesions

“…Despite the highest SNPs for POLB were reported in other African population, the Asian population has the highest SNP for PRKAG2, PRKAB2, and F2 (Table 2). An evidence of TP63 SNPs in radicular cyst was previously reported by Souza et al (177). In the radicular cyst, beta-sitosterol and ethanimidic acid were the only unique metabolites found to provide the enriched metabolic pathways as described in Table 4.…”

Genetic, Cellular and Molecular Aspects involved in Apical Periodontitis

“…Considering the differences in the human DNA sequence, not all individuals have the same response to a certain stimulus or treatment due to differences in the human DNA sequence, which influence the organism's susceptibility to disease and its responses to the environment (15,16). These variations are considered normal but when found in more than 1% of the population are called genetic polymorphisms (15,(17)(18)(19).…”