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Evaluate the association of genetic variants of the interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes with periodontitis. The study involved 117 individuals with periodontitis and 389 without periodontitis, all Brazilians, miscegenated. Individuals with periodontitis presented at least 4 teeth with ≥ 1 site with probing depth ≥ 4 mm; clinical attachment level ≥ 3 mm on the same site and bleeding upon stimulus. Genotyping was performed using the Infinium Multi-Ethnic AMR/AFR-8 Bead Chip focused on Hispanic and African American populations with approximately 2 million markers of the human genome. Multivariate logistic regression was performed to identify associations in additive, dominant and recessive models adjusted for covariates age, obesity, mouth breathing, flossing, asthma, and ancestry. In IFI16 , the rs75985579-A is positively associated with periodontitis in the additive (Odds Ratio adjusted (ORadjusted) 2.65, 95% confidence interval (CI):1.25–5.60, p value: 0.007) and dominant models (ORadjusted 2.56, 95%CI:1.13–5.81, p value: 0.017). In AIM2 , the rs76457189-G, is associated negatively with periodontitis in two genetic models evaluated, additive (ORadjusted 0.21, 95%CI:0.05–0.94, p value: 0.022) and dominant (ORadjusted 0.21, 95%CI:0.05–0.94, p value: 0.022). These results have shown that variants in the IFI16 and AIM2 genes are associated with periodontitis. Individuals with at least one A (adenine) allele of the rs75985579 (IFI16) are more than twice as likely to have periodontitis, while individuals with the G (guanine) allele of rs76457189 (AIM2) are less likely to be diagnosed with periodontitis, providing a negative association with periodontitis. • Genetic variant in the IFI16 gene influences the production of eotaxin-1. • The presence of both studied alleles quadruples the chances of periodontitis. • Genetic variants in the IFI16 and AIM2 genes are associated with periodontitis. [ABSTRACT FROM AUTHOR]