Decreased Levels of <i>PIAS</i> Genes in Periodontitis: A Pilot Study for Finding Possible Contribution of Immune-Related Pathways in Periodontitis

Background: Protein inhibitor of activated STAT (PIAS) refers to a group of molecules that regulate the transcription of several genes, particularly those involved in modulating immune responses and cytokine production. Objectives: Given that the development of periodontitis is associated with abnormal levels of several cytokines, we evaluated the potential contribution of PIAS genes to the etiology of periodontitis by assessing the transcript levels of these genes in the blood and tissue of affected patients. We also aimed to assess the biomarker roles of these genes. Methods: In this case-control study, we employed consecutive sampling and included every subject meeting the inclusion criteria over a six-month period. The study comprised 26 cases and 28 controls referred to clinics affiliated with Hamadan University of Medical Sciences during 2022. Gene expression was assessed using quantitative real-time PCR. Differences in the mean expression levels of genes were evaluated using the t-test or Mann-Whitney U test. Results: The PIAS1 was under-expressed in blood samples obtained from patients compared to control samples (Ratio of mean expression [RME] = 0.49, P = 0.04). However, sex-based expression assays revealed no significant difference in its expression between patients and controls (P = 0.11 and 0.32 for females and males, respectively). The PIAS2 levels tended to be lower in total cases (RME = 0.50, P = 0.05) and in male patients compared to controls (RME = 0.37, P = 0.05). Conversely, PIAS3 expression tended to be increased in patients' tissues (RME = 2.12, P = 0.05). Finally, PIAS4 had lower transcript levels in the blood of patients versus controls (RME = 0.49, P = 0.03), and in female patients versus matched controls (RME = 0.36, P = 0.03). Conclusions: Overall, the altered levels of PIAS genes in the circulation of these patients may explain abnormalities in cytokine levels and immune function in the context of periodontitis.