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Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil

Hepatitis C is considered a major public health problem caused by the hepatitis C virus (HCV). Viral infections are known to induce production of IL1β through the signaling pathway of inflammasomes. Emerging evidences suggest that Inflammasome genes may influence the immune response against HCV as t...

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Autores principales: Toro, Diana Mota, Ramasawmy, Rajendranath, Silva Neto, Pedro Vieira, Pereira, Grenda Leite, Sarmento, Priscila Santos, Dray, Hanna Lara Silva Negreiros, Sousa, Keyla Santos, Affonso, Juliana Santos, Silva, Jéssica Albuquerque, Garcia, Nadja Pinto, Barbieri, Marilú Victória, Victória, Flamir Silva, Donadi, Eduardo Antônio, Costa, Allyson Guimarães, Ogusku, Mauricio Morishi, Sadahiro, Aya, Tarragô, Andréa Monteiro, Malheiro, Adriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221483/
https://www.ncbi.nlm.nih.gov/pubmed/34161370
http://dx.doi.org/10.1371/journal.pone.0253470
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author Toro, Diana Mota
Ramasawmy, Rajendranath
Silva Neto, Pedro Vieira
Pereira, Grenda Leite
Sarmento, Priscila Santos
Dray, Hanna Lara Silva Negreiros
Sousa, Keyla Santos
Affonso, Juliana Santos
Silva, Jéssica Albuquerque
Garcia, Nadja Pinto
Barbieri, Marilú Victória
Victória, Flamir Silva
Donadi, Eduardo Antônio
Costa, Allyson Guimarães
Ogusku, Mauricio Morishi
Sadahiro, Aya
Tarragô, Andréa Monteiro
Malheiro, Adriana
author_facet Toro, Diana Mota
Ramasawmy, Rajendranath
Silva Neto, Pedro Vieira
Pereira, Grenda Leite
Sarmento, Priscila Santos
Dray, Hanna Lara Silva Negreiros
Sousa, Keyla Santos
Affonso, Juliana Santos
Silva, Jéssica Albuquerque
Garcia, Nadja Pinto
Barbieri, Marilú Victória
Victória, Flamir Silva
Donadi, Eduardo Antônio
Costa, Allyson Guimarães
Ogusku, Mauricio Morishi
Sadahiro, Aya
Tarragô, Andréa Monteiro
Malheiro, Adriana
author_sort Toro, Diana Mota
collection PubMed
description Hepatitis C is considered a major public health problem caused by the hepatitis C virus (HCV). Viral infections are known to induce production of IL1β through the signaling pathway of inflammasomes. Emerging evidences suggest that Inflammasome genes may influence the immune response against HCV as the host genetic background may contribute to the balance between acute and chronic inflammation. We investigated in 151 patients with chronic hepatitis C and 206 healthy blood donors’ individuals (HD). Polymorphisms in the IL1B and IL18 genes were genotyped by PCR-RFLP, while NLRP3, CARD8, CTSB and AIM2 by RT- PCR. Serum assay of IL-1β cytokine was performed by ELISA. 84 patients presented mild fibrosis (<F2) and 67 advanced fibrosis (≥ F2). Among the HD individuals the NLRP3-rs10754558 C/C genotype correlated with higher IL-1β levels compared to the G/G genotype. Similar pattern was observed in patients with hepatitis C, mean circulating IL-1β levels were 21,96 ± 4.5 and 10,62 ± 3.3pg/mL among the C/C and G/G genotypes, respectively. This pattern holds even after stratification of the patients into mild fibrosis and advanced fibrosis, demonstrating that the NLRP3-rs10754558 or another polymorphism in linkage disequilibrium with it possibly has an influence on the processing of pro-IL-1β. Notably, higher levels of IL-1β (Mann–Whitney test, p<0.0001) were observed among patients (mean ± SEM: 19,24 ±3.pg/mL) when compared with controls (mean ± SEM: 11,80 ±1.0pg/mL). Gene-gene interaction showed that individuals heterogyzotes for both CARD8-rs2009373 and IL1B-rs16944 are less prone to hepatitis C development (p(adj) = 0.039). Similarly, herozygote carriers for CTSB-rs1692816 and AIM2-rs1103577 (p(adj) = 0.008) or for IL18-rs187238 and NLRP3-rs10754558 (p(adj) = 0.005), have less chances to the development of hepatitis C. However, between subgroups of <F2 and ≥F2, individuals homozygous for the T allele of CARD8-rs2009373 and heterozygous for IL18-rs187238 (p(adj) = 0.028), have mild form of fibrosis.
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spelling pubmed-82214832021-07-07 Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil Toro, Diana Mota Ramasawmy, Rajendranath Silva Neto, Pedro Vieira Pereira, Grenda Leite Sarmento, Priscila Santos Dray, Hanna Lara Silva Negreiros Sousa, Keyla Santos Affonso, Juliana Santos Silva, Jéssica Albuquerque Garcia, Nadja Pinto Barbieri, Marilú Victória Victória, Flamir Silva Donadi, Eduardo Antônio Costa, Allyson Guimarães Ogusku, Mauricio Morishi Sadahiro, Aya Tarragô, Andréa Monteiro Malheiro, Adriana PLoS One Research Article Hepatitis C is considered a major public health problem caused by the hepatitis C virus (HCV). Viral infections are known to induce production of IL1β through the signaling pathway of inflammasomes. Emerging evidences suggest that Inflammasome genes may influence the immune response against HCV as the host genetic background may contribute to the balance between acute and chronic inflammation. We investigated in 151 patients with chronic hepatitis C and 206 healthy blood donors’ individuals (HD). Polymorphisms in the IL1B and IL18 genes were genotyped by PCR-RFLP, while NLRP3, CARD8, CTSB and AIM2 by RT- PCR. Serum assay of IL-1β cytokine was performed by ELISA. 84 patients presented mild fibrosis (<F2) and 67 advanced fibrosis (≥ F2). Among the HD individuals the NLRP3-rs10754558 C/C genotype correlated with higher IL-1β levels compared to the G/G genotype. Similar pattern was observed in patients with hepatitis C, mean circulating IL-1β levels were 21,96 ± 4.5 and 10,62 ± 3.3pg/mL among the C/C and G/G genotypes, respectively. This pattern holds even after stratification of the patients into mild fibrosis and advanced fibrosis, demonstrating that the NLRP3-rs10754558 or another polymorphism in linkage disequilibrium with it possibly has an influence on the processing of pro-IL-1β. Notably, higher levels of IL-1β (Mann–Whitney test, p<0.0001) were observed among patients (mean ± SEM: 19,24 ±3.pg/mL) when compared with controls (mean ± SEM: 11,80 ±1.0pg/mL). Gene-gene interaction showed that individuals heterogyzotes for both CARD8-rs2009373 and IL1B-rs16944 are less prone to hepatitis C development (p(adj) = 0.039). Similarly, herozygote carriers for CTSB-rs1692816 and AIM2-rs1103577 (p(adj) = 0.008) or for IL18-rs187238 and NLRP3-rs10754558 (p(adj) = 0.005), have less chances to the development of hepatitis C. However, between subgroups of <F2 and ≥F2, individuals homozygous for the T allele of CARD8-rs2009373 and heterozygous for IL18-rs187238 (p(adj) = 0.028), have mild form of fibrosis. Public Library of Science 2021-06-23 /pmc/articles/PMC8221483/ /pubmed/34161370 http://dx.doi.org/10.1371/journal.pone.0253470 Text en © 2021 Toro et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Toro, Diana Mota
Ramasawmy, Rajendranath
Silva Neto, Pedro Vieira
Pereira, Grenda Leite
Sarmento, Priscila Santos
Dray, Hanna Lara Silva Negreiros
Sousa, Keyla Santos
Affonso, Juliana Santos
Silva, Jéssica Albuquerque
Garcia, Nadja Pinto
Barbieri, Marilú Victória
Victória, Flamir Silva
Donadi, Eduardo Antônio
Costa, Allyson Guimarães
Ogusku, Mauricio Morishi
Sadahiro, Aya
Tarragô, Andréa Monteiro
Malheiro, Adriana
Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil
title Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil
title_full Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil
title_fullStr Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil
title_full_unstemmed Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil
title_short Inflammasome genes polymorphisms may influence the development of hepatitis C in the Amazonas, Brazil
title_sort inflammasome genes polymorphisms may influence the development of hepatitis c in the amazonas, brazil
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221483/
https://www.ncbi.nlm.nih.gov/pubmed/34161370
http://dx.doi.org/10.1371/journal.pone.0253470
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