Variants in interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes that modulate inflammatory response are associated with periodontitis.

OBJECTIVE: Evaluate the association of genetic variants of the interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes with periodontitis. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The role of IL10 and IL17 gene polymorphisms in treatment response in children and adolescents with severe asthma / O papel de polimorfismos dos genes IL10 e IL17 na resposta ao tratamento em crianças e adolescentes com asma grave

ABSTRACT Objective: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. Methods: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). Results: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a b2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. Conclusions: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

RESUMO Objetivo: Determinar se existe relação entre polimorfismos dos genes IL10 e IL17 e controle da asma grave e reversibilidade com broncodilatador em crianças e adolescentes com asma grave. Métodos: Estudo transversal, aninhado em um estudo prospectivo de coorte com pacientes com asma grave. Foram avaliados dois desfechos: controle da asma e reversibilidade com broncodilatador. Extraímos DNA do sangue periférico e genotipamos três polimorfismos de nucleotídeo único: rs3819024 e rs2275913 no gene IL17A e rs3024498 no gene IL10. Para as análises de associação, realizamos regressão logística em três modelos genéticos (alélico, aditivo e dominante). Resultados: O alelo C do polimorfismo rs3024498 do gene IL10 apresentou relação com asma que permaneceu descontrolada mesmo com tratamento regular (p = 0,02). No entanto, o alelo G do polimorfismo rs3819024 do gene IL17A apresentou relação com ausência de resposta ao estímulo com b2-agonista. O polimorfismo rs2275913 do gene IL17A não apresentou relação com controle da asma ou reversibilidade com broncodilatador. Conclusões: Em pacientes pediátricos com asma grave, o polimorfismo do gene IL10 parece estar relacionado com ausência de controle clínico, ao passo que o polimorfismo do gene IL17A parece estar relacionado com pior resposta ao broncodilatador. O conhecimento a respeito do envolvimento desses polimorfismos abre perspectivas futuras para estudos farmacogenéticos e para a implantação de manejo terapêutico individualizado da asma grave em pacientes pediátricos.