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Artigo Acesso aberto Produção Nacional Revisado por pares
BIBTEX RIS

Polymorphisms in interferon pathway genes and risk of Mycobacterium tuberculosis infection in contacts of tuberculosis cases in Brazil

2019; Elsevier BV; Volume: 92; Linguagem: Inglês

10.1016/j.ijid.2019.12.013

ISSN

1878-3511

Autores

Juan M. Cubillos-Angulo, María B. Arriaga, Mayla Gabryele Miranda de Melo, Elisângela Silva, Lucia Elena Alvarado-Arnez, Alexandre S. de Almeida, Milton Ozório Moraes, Adriana S. R. Moreira, José Roberto Lapa e Silva, Kiyoshi F. Fukutani, Timothy R. Sterling, Thomas R. Hawn, Afrânio Lineu Kritski, Martha Maria Oliveira, Bruno B. Andrade,

Tópico(s)

Mycobacterium research and diagnosis

Resumo

BackgroundHost 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.MethodsWe 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.ResultsAmong 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).ConclusionsPolymorphisms in PYHIN1-IFI16-AIM2 rs1633256, rs1101998 and in IRF7 rs11246213 were associated with altered susceptibility to Mtb infection in this Brazilian cohort.

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