[HTML][HTML] Polymorphisms in interferon pathway genes and risk of Mycobacterium tuberculosis infection in contacts of tuberculosis cases in Brazil
JM Cubillos-Angulo, MB Arriaga, MGM Melo… - International Journal of …, 2020 - Elsevier
International Journal of Infectious Diseases, 2020•Elsevier
Background 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 …
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 …
Background
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.
Elsevier