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Association of genetic polymorphisms with resistance and susceptibility phenotypes to chronic inflammatory osteolytic periapical and periodontal lesions

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Ian Franco Cavalla Ruiz
Total Authors: 1
Document type: Doctoral Thesis
Press: Bauru.
Institution: Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru (FOB/SDB)
Defense date:
Examining board members:
Gustavo Pompermaier Garlet; Ana Carla Pereira Latini; Lucimara Teixeira das Neves; Lucas Trevizani Rasmussen
Advisor: Gustavo Pompermaier Garlet

Chronic periodontitis and apical periodontitis are infectious diseases characterized by the inflammatory destruction of teeth-supporting tissues. The clinical presentation of these diseases is the result of the interaction between the infecting microorganisms and the hosts defense mechanisms, constituting the host/pathogen barrier. Genetic variations are associated with differential susceptibility profiles, modulating simultaneously the patterns of infection and immune response. Therefore, we investigated the association of selected genetic variations with phenotypes of resistance or susceptibility to periodontal and periapical inflammatory bone resorption, as well as with changes in the sub gingival microbial profile and hosts response biomarkers. The polymorphism rs4794067 (gene TBX21) proved significantly associated with increased risk to suffer periodontitis. Polymorphic allele-carriers demonstrated increased expression of T-bet. IFN- expression and bacterial load proved unaltered by genotype differences. The mutation rs333 (a.k.a. CCR532, in gene CCR5) demonstrated a protective effect against chronic periodontitis. Heterozygous subjects exhibited decreased TNF- expression. The genetic mutation was unrelated to changes in the bacterial load of putative periodontal pathogens. The polymorphisms rs2521634 (gene NPY), rs10010758 (gene TBC1D), rs6667202 (gene IL10), and rs10043775 (gene TBXO38) proved associated with significant changes in the composition of the subgingival biofilm in chronic periodontitis patients. For apical periodontitis we employed an unbiased biomarker screening strategy based in 2D diferential electrophoresis in tandem with mass spectrometry. Among the biomarkers that proved significantly modulated, we discover a substantial upregulation of HSP27 and SERPINB1. Both proteins were preferentially localized in the cytoplasm of epithelial cells in the epithelium lining the cystic cavity and the epithelial chords of epithelized granulomas. Additionally, SERPINB1 was expressed in infiltrating polymorph nuclear neutrophils. The expression of HSP27 and SERPINB1 demonstrated a negative correlation with acute inflammation biomarkers. Overall, these genes and protein biomarkers may be promissory targets to predict the risk profile for periodontal and periapical inflammatory bone resorption. (AU)

FAPESP's process: 14/03276-0 - Influence of genetic polymorphisms in the colonization/recolonization patterns in chronic periodontitis patients
Grantee:Ian Franco Cavalla Ruiz
Support Opportunities: Scholarships in Brazil - Doctorate