Determinantes genéticas em genes de interleucinas e suas possíveis associações com o risco no desenvolvimento de periodontite: resultados de metanálises convencionais e com abordagem Bayesiana

Abstract

Periodontitis is an inflammatory disease with a high prevalence in dentistry, which its pathophysiology is characterized by the role of inflammatory mediators that culminates in a degradation of the support tissues around the teeth. Genetic variations in interleukin (IL) genes receive attention in the context of factors related with the increased risk of periodontitis developing. Both case studies / control of polymorphisms in cytokine genes such as IL-2 or molecules participating in epigenetic mechanisms such as the INK4 antisense non-coding RNA (ANRIL) or meta-analysis studies on IL1A, 1B, 1RN, 4, 6 genetic variants among other that determine the association with periodontitis. However, contradictory results on the association between polymorphisms in the IL2 and ANRIL genes are available in the literature, as well as the likelihood of false-positive findings in the analyses on polymorphisms in the IL genes and risk of periodontitis. Thus, in view of these findings, the aim of this study is to perform meta-analyses on genetic data on IL2 and ANRIL and validates the findings on polymorphisms in IL genes and chronic periodontitis through the Bayesian approach. For this, a systematic search of databases was carried out for studies previously published in 2019 following the inclusion of studies. Data were extracted from included articles with subsequent statistical assessment using the Review Manager and Comprehensive Meta-Analysis software with heterogeneity calculations (I²), Odds Ratio (OR) and the publication bias tests with Funnel-plot graphic. In all evaluations, the value of P<0.05 was considered as significant. In the Bayesian approach, calculations of False Positive Rate Probability (FPRP) and Bayesian False Discovery Probability (BFDP) were performed to detect the noteworthiness of the findings from the meta-analyzes available in the literature with a value of P<0.02 for FPRP and P<0.08 for BDFP. As results, five studies were found for the -330 T/G polymorphism in the IL2 gene and chronic periodontitis, 12 studies for the rs1333048 polymorphism in the ANRIL gene and periodontitis and 9 meta-analysis studies on different polymorphisms in the IL genes. There was no significant association for the polymorphism in the IL2 gene and the risk of periodontitis (OR = 2.07, P = 0.15), but a significant association between the polymorphism in the ANRIL gene and the risk of disease (OR = 1.24, P<0.00001). All the genetic variants used in the analyses submitted to the Bayesian approach, including the polymorphisms rs1800587 in IL1A and rs1143634, no IL1B genes were "noteworthy". In conclusion, this study showed the relationship between polymorphisms in the IL2 and ANRIL genes with periodontitis, as well as the revalidation of data on meta-analyses focused on polymorphisms in the IL1A and 1B genes with the risk of developing periodontitis demonstrating those as biomarkers for the susceptibility to the disease.