Please use this identifier to cite or link to this item: https://repositorio.inpa.gov.br/handle/1/37677
Title: Single nucleotide variants in AIM2 - absent in the melanoma 2 gene (rs1103577) associated with protection against tuberculosis
Authors: Figueira, Mariana Brasil De Andrade
Lima, Dhêmerson Souza de
Boechat, Antonio Luiz
Nascimento Filho, Milton Gomes do
Antunes, Irineide Assumpção
Matsuda, Joycenéa Da Silva
Ribeiro, Thaís Rodrigues De Albuquerque
Felix, Luana Sousa
Gonçalves, Ariane Senna Fonseca
Costa, Allyson Guimarães da
Ramasawmy, Rajendranath
Pontillo, Alessandra
Mauricio Morishi, Ogusku
Aya, Sadahiro
Keywords: AIM2
CARD8
CTSB
inflamassoma
SNV
tuberculosis
Issue Date: 2021
metadata.dc.publisher.journal: Frontiers in Immunology
metadata.dc.relation.ispartof: Volume 12; Number 604975
metadata.dc.description.resumo: Tuberculosis (TB) remains a serious public health burden worldwide. TB is an infectious disease caused by the Mycobacterium tuberculosis Complex. Innate immune response is critical for controlling mycobacterial infection. NOD-like receptor pyrin domain containing 3/ absent in melanoma 2 (NLRP3/AIM2) inflammasomes are suggested to play an important role in TB. NLRP3/AIM2 mediate the release of pro-inflammatory cytokines IL-1β and IL-18 to control M. tuberculosis infection. Variants of genes involved in inflammasomes may contribute to elucidation of host immune responses to TB infection. The present study evaluated single-nucleotide variants (SNVs) in inflammasome genes AIM2 (rs1103577), CARD8 (rs2009373), and CTSB (rs1692816) in 401 patients with pulmonary TB (PTB), 133 patients with extrapulmonary TB (EPTB), and 366 healthy control (HC) subjects with no history of TB residing in the Amazonas state. Quantitative Real Time PCR was performed for allelic discrimination. The SNV of AIM2 (rs1103577) is associated with protection for PTB (padj: 0.033, ORadj: 0.69, 95% CI: 0.49-0.97). CTSB (rs1692816) is associated with reduced risk for EPTB when compared with PTB (padj: 0.034, ORadj: 0.50, 95% CI: 0.27-0.94). Serum IL-1β concentrations were higher in patients with PTB than those in HCs (p = 0,0003). The SNV rs1103577 of AIM2 appeared to influence IL-1β release. In a dominant model, individuals with the CC genotype (mean 3.78 ± SD 0.81) appeared to have a higher level of IL-1β compared to carriers of the T allele (mean 3.45 ± SD 0.84) among the patients with PTB (p = 0,0040). We found that SNVs of AIM2 and CTSB were associated with TB, and the mechanisms involved in this process require further study. © Copyright © 2021 Figueira, de Lima, Boechat, Filho, Antunes, Matsuda, Ribeiro, Felix, Gonçalves, da Costa, Ramasawmy, Pontillo, Ogusku and Sadahiro.
metadata.dc.identifier.doi: 10.3389/fimmu.2021.604975
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