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In view of the need for surgical intervention (cases assessed with a CBCTPAI score of 4 and 5, with the presence of symptoms), 20 patients were selected for endodontic surgery, which was planned using cone beam computed tomography images. Initially, saliva was collected as a source of genomic DNA, and the individuals were genotyped for\n SOCS\u20101<\/jats:italic>\n ,\n TNF\u2010\u03b1<\/jats:italic>\n and\n RANKL<\/jats:italic>\n polymorphisms by real\u2010time PCR. After collecting the biological material, the periapical lesions obtained were subjected to analysis of gene expression levels for\n RANK<\/jats:italic>\n ,\n RANKL<\/jats:italic>\n ,\n TNFRSF1, SOCS\u20101, IL\u201010<\/jats:italic>\n ,\n IL\u20101\u03b2<\/jats:italic>\n and\n TNF\u2010\u03b1<\/jats:italic>\n , and histopathological evaluation for characterisation and differentiation into periapical granulomas and cysts; immunohistochemical evaluation for SOCS\u20101 and IL\u20101\u03b2 protein labeling; and microbiological analysis to identify the microorganisms involved in persistent periapical infection. The relative mRNA expression values of each gene in each group, according with genotypes in different SNPs, were analysed using one\u2010way analysis of variance followed by Tukey's post\u2010test or\n T<\/jats:italic>\n \u2010test (\n \u03b1<\/jats:italic>\n \u2009=\u20095%).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Different expression values of the genes evaluated were observed according to the genotypes of the polymorphisms evaluated in relation to PAP (\n p<\/jats:italic>\n \u2009<\u20090.05). Among the cases submitted for histopathological evaluation, 66.7% were diagnosed as periapical granuloma and 33.3% as periapical cyst. Immunohistochemical analysis showed strong positivity for SOCS\u20101 and IL\u20101\u03b2 in the lesions classified as periapical cyst, while the lesions diagnosed as periapical granuloma were not labelled. In the microbiological analysis, four different species of bacteria were isolated:\n \n Pseudomonas aeruginosa<\/jats:italic>\n <\/jats:styled-content>\n ,\n \n Staphylococcus epidermidis<\/jats:italic>\n <\/jats:styled-content>\n ,\n \n Enterococcus faecalis<\/jats:italic>\n <\/jats:styled-content>\n and\n \n Bacillus cereus<\/jats:italic>\n <\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This exploratory study indicates that genetic polymorphisms can modulate gene expression and protein activity in PAP, shaping the host's inflammatory and reparative response. These findings highlight their potential as biomarkers and establish a basis for future translational studies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/iej.70070","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T04:33:36Z","timestamp":1765600416000},"page":"486-501","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring Persistent Apical Periodontitis in Humans: Integrative Genetic, Histological and Microbiological Perspectives for Translational Research"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-5730","authenticated-orcid":false,"given":"Igor Bassi Ferreira","family":"Petean","sequence":"first","affiliation":[{"name":"Department of Restorative Dentistry, School of Dentistry of Ribeir\u00e3o Preto University of S\u00e3o Paulo S\u00e3o Paulo 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