Impact of Slc11a1 gene variants on response standards of the host and the determination of phenotypes resistance and susceptibility to periodontal diseases

Abstract

Periodontitis is initiated by accumulation of bacteria on the surface of the teeth and host factors are involved in the determination of susceptibility/resistance to microbial challenge, being such factors under the influence of multiple genetic loci. Studies in humans and in experimental models have supported the influence of genes in the determination of susceptibility/resistance phenotypes to periodontitis. Among these genes, Slc11a1, whose pleiotropic functions include regulation of macrophage and lymphocyte activity; presents a potential role in the modulation of resistance/ susceptibility phenotypes to periodontal diseases. In this context, our group demonstrated that AIRmax and AIRmin mice strains, which carry different R and S variants of the alleles of Slc11a1, associated with different patterns of immune and inflammatory response, present distinct phenotypes of resistance/susceptibility to experimental periodontitis. In order to correlate the genetic polymorphisms rs17228995, rs17235409, rs2290708, rs2695343, rs3731865 of the Slc11a1 gene (selected to represent all variations in the gene, in the view of the linkage disequilibrium pattern) in Slc11a1 with the phenotypic profiles of resistance/susceptibility to periodontal diseases (Garlet et al., 2012, Cavalla et al., 2015). To do so, we will use samples from an existing database of 197 patients with chronic periodontitis, 354 healthy individuals, and 193 individuals with chronic gingivitis for genetic association analyzes and correlations with the clinical characteristics of periodontitis. (N and SNPs previously tested for statistical power of the sample considering disease prevalence, allele frequency and N of the experimental groups) and subgroups composed of 75 patients with chronic periodontitis and 50 healthy individuals, to be analyzed for possible associations between the target SNP genotype and the expression of inflammatory and immunological markers. Establishing a correlation between genotypes, clinical parameters and immune and inflammatory response patterns will certainly contribute to a better understanding of individual risk determinants, helping to identify risk and serving as a basis for the development of new prevention and control strategies. Treatment of periodontal diseases. (AU)