Single-Nucleotide Variants in the AIM2 – Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for Tuberculosis
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)...
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.604975/full |
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| author | Mariana Brasil de Andrade Figueira Mariana Brasil de Andrade Figueira Dhêmerson Souza de Lima Antonio Luiz Boechat Antonio Luiz Boechat Milton Gomes do Nascimento Filho Irineide Assumpção Antunes Joycenéa da Silva Matsuda Thaís Rodrigues de Albuquerque Ribeiro Luana Sousa Felix Ariane Senna Fonseca Gonçalves Allyson Guimarães da Costa Allyson Guimarães da Costa Rajendranath Ramasawmy Rajendranath Ramasawmy Rajendranath Ramasawmy Alessandra Pontillo Mauricio Morishi Ogusku Aya Sadahiro Aya Sadahiro |
| author_facet | Mariana Brasil de Andrade Figueira Mariana Brasil de Andrade Figueira Dhêmerson Souza de Lima Antonio Luiz Boechat Antonio Luiz Boechat Milton Gomes do Nascimento Filho Irineide Assumpção Antunes Joycenéa da Silva Matsuda Thaís Rodrigues de Albuquerque Ribeiro Luana Sousa Felix Ariane Senna Fonseca Gonçalves Allyson Guimarães da Costa Allyson Guimarães da Costa Rajendranath Ramasawmy Rajendranath Ramasawmy Rajendranath Ramasawmy Alessandra Pontillo Mauricio Morishi Ogusku Aya Sadahiro Aya Sadahiro |
| author_sort | Mariana Brasil de Andrade Figueira |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T08:12:55Z |
| format | Article |
| id | doaj.art-5afca8f0521a4c6d81f745054d56062f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T08:12:55Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5afca8f0521a4c6d81f745054d56062f2022-12-21T20:29:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.604975604975Single-Nucleotide Variants in the AIM2 – Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for TuberculosisMariana Brasil de Andrade Figueira0Mariana Brasil de Andrade Figueira1Dhêmerson Souza de Lima2Antonio Luiz Boechat3Antonio Luiz Boechat4Milton Gomes do Nascimento Filho5Irineide Assumpção Antunes6Joycenéa da Silva Matsuda7Thaís Rodrigues de Albuquerque Ribeiro8Luana Sousa Felix9Ariane Senna Fonseca Gonçalves10Allyson Guimarães da Costa11Allyson Guimarães da Costa12Rajendranath Ramasawmy13Rajendranath Ramasawmy14Rajendranath Ramasawmy15Alessandra Pontillo16Mauricio Morishi Ogusku17Aya Sadahiro18Aya Sadahiro19Laboratório de Imunologia Molecular, Departamento de Parasitologia, Universidade Federal do Amazonas (UFAM), Manaus, BrazilPrograma de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, Manaus, BrazilLaboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas (ICB), Universidade de São Paulo (USP), São Paulo, BrazilLaboratório de Imunologia Molecular, Departamento de Parasitologia, Universidade Federal do Amazonas (UFAM), Manaus, BrazilPrograma de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, Manaus, BrazilLaboratório de Imunologia Molecular, Departamento de Parasitologia, Universidade Federal do Amazonas (UFAM), Manaus, BrazilPoliclínica Cardoso Fontes – Secretaria de Estado da Saúde do Amazonas-SUSAM, Manaus, BrazilPoliclínica Cardoso Fontes – Secretaria de Estado da Saúde do Amazonas-SUSAM, Manaus, BrazilLaboratório de Imunologia Molecular, Departamento de Parasitologia, Universidade Federal do Amazonas (UFAM), Manaus, BrazilLaboratório de Imunologia Molecular, Departamento de Parasitologia, Universidade Federal do Amazonas (UFAM), Manaus, BrazilLaboratório de Imunologia Molecular, Departamento de Parasitologia, Universidade Federal do Amazonas (UFAM), Manaus, BrazilPrograma de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, Manaus, BrazilDiretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, BrazilPrograma de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, Manaus, BrazilInstituto de Pesquisa Clínica Carlos Borborema, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, BrazilFaculdade de Medicina Nilton Lins, Universidade Nilton Lins, Manaus, BrazilLaboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas (ICB), Universidade de São Paulo (USP), São Paulo, BrazilLaboratório de Micobacteriologia, Instituto Nacional de Pesquisas da Amazônia (INPA), Manaus, BrazilLaboratório de Imunologia Molecular, Departamento de Parasitologia, Universidade Federal do Amazonas (UFAM), Manaus, BrazilPrograma de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, Manaus, BrazilTuberculosis (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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.604975/fulltuberculosisinflammasomeSNVAIM2CARD8CTSB |
| spellingShingle | Mariana Brasil de Andrade Figueira Mariana Brasil de Andrade Figueira Dhêmerson Souza de Lima Antonio Luiz Boechat Antonio Luiz Boechat Milton Gomes do Nascimento Filho Irineide Assumpção Antunes Joycenéa da Silva Matsuda Thaís Rodrigues de Albuquerque Ribeiro Luana Sousa Felix Ariane Senna Fonseca Gonçalves Allyson Guimarães da Costa Allyson Guimarães da Costa Rajendranath Ramasawmy Rajendranath Ramasawmy Rajendranath Ramasawmy Alessandra Pontillo Mauricio Morishi Ogusku Aya Sadahiro Aya Sadahiro Single-Nucleotide Variants in the AIM2 – Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for Tuberculosis Frontiers in Immunology tuberculosis inflammasome SNV AIM2 CARD8 CTSB |
| title | Single-Nucleotide Variants in the AIM2 – Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for Tuberculosis |
| title_full | Single-Nucleotide Variants in the AIM2 – Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for Tuberculosis |
| title_fullStr | Single-Nucleotide Variants in the AIM2 – Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for Tuberculosis |
| title_full_unstemmed | Single-Nucleotide Variants in the AIM2 – Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for Tuberculosis |
| title_short | Single-Nucleotide Variants in the AIM2 – Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for Tuberculosis |
| title_sort | single nucleotide variants in the aim2 absent in melanoma 2 gene rs1103577 associated with protection for tuberculosis |
| topic | tuberculosis inflammasome SNV AIM2 CARD8 CTSB |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.604975/full |
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