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POLYMORPHISMS IN INTERFERON PATHWAY GENES AND RISK OF MYCOBACTERIUM TUBERCULOSIS INFECTION IN CONTACTS OF TUBERCULOSIS CASES IN BRAZIL
Cubillos-Angulo, Juan Manuel et al. | Date Issued: 2019
Author
Cubillos-Angulo, Juan Manuel
Arriaga Gutiérrez, María Belen
Melo, Mayla Gabryele Miranda de
Silva, Elisangela Costa da
Arnez, Lucia Elena Alvarado
Almeida, Alexandre S. de
Moraes, Milton Ozório
Moreira, Adriana S. R.
Silva, José Roberto Lapa e
Fukutani, Kiyoshi Ferreira
Sterling, Timothy R.
Hawn, Thomas R.
Kritski, Afrânio Lineu
Oliveira, Martha M.
Andrade, Bruno de Bezerril
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.
Universidade Federal do Rio de Janeiro. Centro de Pesquisas em Doenças Infecciosas e Parasitárias. Laboratório de Micobacteriologia Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Centro de Pesquisas em Doenças Infecciosas e Parasitárias. Laboratório de Micobacteriologia Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Norte Fluminense Darcy Ribeiro. Centro de Biociências e Biotecnologia. Laboratório de Biologia do Reconhecer. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidad Franz Tamayo. Coordinación Nacional de Investigación. La Paz, Bolivia.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.
Vanderbilt University. School of Medicine. Nashville. Department of Medicine. Division of Infectious Diseases. Tennessee, USA.
University of Washington. Department of Medicine. Seattle, WA, USA.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.
University of Washington. Department of Medicine. Seattle, WA, USA.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Vanderbilt University. School of Medicine. Nashville. Department of Medicine. Division of Infectious Diseases. Tennessee, USA / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.
Abstract
Host genetic polymorphisms may be important in determining susceptibility to Mycobacterium tuberculosis (Mtb) infection, but their role is not fully understood. Detection of microbial DNA and activation of type I interferon (IFN) pathways regulate macrophage responses to Mtb infection. Methods: We examined whether seven candidate gene SNPs were associated with tuberculin skin test (TST) positivity in close contacts of microbiologically confirmed pulmonary TB patients in Brazil. Independent associations with TST positivity were tested using multivariable logistic regression (using genotypes and clinical variables) and genetic models. Results: Among 482 contacts of 145 TB index cases, 296 contacts were TST positive. Multivariable regression analysis adjusted for population admixture, age, family relatedness, sex and clinical variables related to increased TB risk demonstrated that SNPs in PYHIN1-IFI16-AIM2 rs1101998 (adjusted OR [aOR]: 3.72; 95%CI = 1.15–12.0; p=0.028) and in PYHIN1-IFI16-AIM2 rs1633256 (aOR= 24.84; 95%CI = 2.26–272.95; p=0.009) were associated with TST positivity in a recessive model. Furthermore, an IRF7 polymorphism (rs11246213) was associated with reduced odds of TST positivity in a dominant model (aOR: 0.50, 95%CI: 0.26-0.93; p=0.029). Conclusions: Polymorphisms in PYHIN1-IFI16-AIM2 rs1633256, rs1101998 and in IRF7 rs11246213 were associated with altered susceptibility to Mtb infection in this Brazilian cohort.
Keywords in Portuguese
Polimorfismo de nucleotídeo único
Teste tuberculínico.
Mycobacterium tuberculosis
 
Keywords
Single nucleotide polymorphism
Tuberculin skin tesT
Mycobacterium tuberculosis
 
Publisher
Elsevier
Citation
CUBILLOS-ANGULO, Juan Manuel et al. Polymorphisms in Interferon Pathway Genes and Risk of Mycobacterium tuberculosis Infection in Contacts of Tuberculosis Cases in Brazil. International Journal of Infectious Diseases, p. 1-27, 2019.
DOI
10.1016/j.ijid.2019.12.013
ISSN
1201-9712