Analysis of periodontitis-associated miRNAs in gingival tissue, gingival crevicular fluid, saliva and blood plasma

Abstract

Objective: Periodontitis (PD) is a chronic inflammatory disease which is associated with multiple systemic comorbidities, including rheumatoid arthritis (RA), meanwhile the etiopathology of PD may be modulated by various factors including microRNA (miRNA). The present study aimed to reveal miRNAs associated with PD in gingival tissue, gingival crevicular fluid (GCF), saliva, plasma and to assess the possible influence of RA.

Design: The cross-sectional study included 30 patients with PD and 31 periodontally healthy participants. A total of 25 participants were additionally diagnosed with RA. Microarray analysis of eight gingival tissue samples was performed and four PD-associated miRNAs were selected: miR-199a-5p, miR-483-5p, miR-3198 and miR-4299. Target miRNAs were further assessed by means of RT-qPCR in 61 gingival tissue samples and corresponding bodily fluids - GCF, saliva and plasma.

Results: The upregulation of miR-199a-5p and downregulation of miR-4299 in gingival tissue was associated with the presence of PD and RA (P < 0.05). GCF level of miR-3198 was higher amongst participants with PD (P = 0.019) and showed a good diagnostic ability (AUC = 0.72, P = 0.008). Increased miR-199a-5p salivary level and decreased miR-199a-5p plasma level were observed amongst patients with worse clinical status of PD (P < 0.05). MiR-3198 and miR-4299 combination in GCF demonstrated AUC value of 0.86 and reached sensitivity of 68 % and specificity of 96 %.

Conclusions: Aberrant expression of miR-199a-5p, miR-483-5p, miR-3198, miR-4299 in gingival tissues is associated with the presence and/or severity of PD. MiR-3198, miR-4299 level in GCF and miR-199a-5p level in plasma strongly correlated with PD, demonstrating significant diagnostic performance.

Keywords: Biomarkers; Circulating miRNAs; Periodontitis; Rheumatoid arthritis.