AUTHOR=Figueira Mariana Brasil de Andrade , de Lima Dhêmerson Souza , Boechat Antonio Luiz , Filho Milton Gomes do Nascimento , Antunes Irineide Assumpção , Matsuda Joycenéa da Silva , Ribeiro Thaís Rodrigues de Albuquerque , Felix Luana Sousa , Gonçalves Ariane Senna Fonseca , da Costa Allyson Guimarães , Ramasawmy Rajendranath , Pontillo Alessandra , Ogusku Mauricio Morishi , Sadahiro Aya 

TITLE=Single-Nucleotide Variants in the AIM2 – Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for Tuberculosis

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.604975

DOI=10.3389/fimmu.2021.604975

ISSN=1664-3224

ABSTRACT=<p>Tuberculosis (TB) remains a serious public health burden worldwide. TB is an infectious disease caused by the <italic>Mycobacterium tuberculosis</italic> 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 <italic>M. tuberculosis</italic> 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 <italic>AIM2</italic> (rs1103577), <italic>CARD8</italic> (rs2009373), and <italic>CTSB</italic> (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 <italic>AIM2</italic> (rs1103577) is associated with protection for PTB (<italic>p</italic>adj: 0.033, ORadj: 0.69, 95% CI: 0.49-0.97). <italic>CTSB</italic> (rs1692816) is associated with reduced risk for EPTB when compared with PTB (<italic>p</italic>adj: 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 (<italic>p</italic> = 0,0003). The SNV rs1103577 of <italic>AIM2</italic> 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 (<italic>p</italic> = 0,0040). We found that SNVs of <italic>AIM2</italic> and <italic>CTSB</italic> were associated with TB, and the mechanisms involved in this process require further study.</p>