The role of IL10 and IL17 gene polymorphisms in treatment response in children and adolescents with severe asthma

Author:

Isadora Ribeiro Vieira1 Mariana1ORCID,Versiani Nunes Pinheiro de Queiroz3 Mônica2ORCID,Borges Rabelo de Santana2 Maria3ORCID,dos Santos Silva2 Hatilla3ORCID,Oliveira2 Almirane3ORCID,Alexandrina Viana Figueiredo2 Camila3ORCID,Martín Tarazona Santos4 Eduardo4ORCID,dos Santos Costa2 Ryan3ORCID,Maria de Lima Belizário Facury Lasmar1,2 Laura5ORCID

Affiliation:

1. 1. Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte (MG) Brasil.

2. 3. Programa de Pós-Graduação em Imunologia, Departamento de Biorregulação, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador (BA) Brasil.

3. 2. Departamento de Pediatria, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte (MG) Brasil.

4. 4. Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte (MG) Brasil.

5. 1. Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte (MG) Brasil. 2. Departamento de Pediatria, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte (MG) Brasil.

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 ß2 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.

Publisher

Sociedade Brasileira de Pneumologia e Tisiologia

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