Influência de variantes genéticas dos genes SEPT7 e FMN1 na periodontite

Abstract

Introduction: Periodontitis is an inflammatory disease caused by the interaction between the dysbiotic bacterial biofilm and the host immune response that affects the tissues of dental support, which can lead to loss of dental unit. As it is a complex, multifactorial, and polygenic disease, genetic, environmental, and systemic aspects may be involved. Genetic variants can influence the immune response and other mechanisms, such as those that can be regulated by variants of the SEPT7 and FMN1 genes. These genes participate in the process of cell division, microtubule dynamics, and actin filaments. Goal: To investigate the association of genetic variants in the SEPT7 and FMN1 genes with periodontitis. Methods: A cross-sectional study developed with 506 participants in the Asthma Control Program in Bahia, classified as presence (n=117) or absence (n=389) of periodontitis. An interview was carried out to obtain data and a complete oral examination. For the diagnosis of periodontitis, individuals had at least 4 teeth with ≥ 1 site with probing depth ≥ 4 mm; clinical attachment level ≥ 3 mm, and bleeding on stimulus in the same location. Genotyping was performed by using the Illumina Infinium Multi-Ethnic AMR/AFR-8 kit. The association analysis was carried out by using the Plink 1.9 software using multivariate logistic regression adjusted for the covariates of age, obesity, mouth breathing, dental flossing, asthma, and ancestry. The NCBI, RegulomeDB, Haploview 4.2, rSNPBase, and Gtex platforms were analyzed in silico analyses. Results: 5 SNVs from the SEPT7 gene were positively associated with periodontitis, and of the 15 SNVs from the FMN1 gene, 8 were positively associated and 7 negatively. Outcomes related to age and flossing were observed, in which having a certain SNV may be positively or negatively associated with the development of periodontitis. The cytokines IL-5 and IL-13 were associated with SEPT7 SNVs (rs12532523 and rs6462629); and FMN1 variants were associated with the cytokines’ interferon-gamma, IL-17A, IL-10, and IL-5. Discussion: First association study of variants of the SEPT7 and FMN1 candidate genes with periodontitis. Genetic variants of these genes were associated with periodontitis in a genome-wide scanning study (GWAS) in a Brazilian population, with limitations regarding comparisons with other studies due to the scarcity of reports on these genes and the disease in question. Gene-environment interaction analysis revealed that there is a relationship between studied genetic variants and the development of periodontitis based on covariates such as age and dental floss use. Conclusion: Variants in the SEPT7 and FMN1 genes were associated with periodontitis, reinforcing the influence of genetics on the development of periodontitis and the need for new studies with a larger sample size that corroborate the data found.