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Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma
A higher Th17-immune response characterises obesity and obesity-related asthma phenotype. Nevertheless, obesity-related asthma has a more significant Th17-immune response than obesity alone. Retinoid-related orphan receptor C (RORC) is the essential transcription factor for Th17 polarisation. Previo...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9798174/ https://www.ncbi.nlm.nih.gov/pubmed/36590520 http://dx.doi.org/10.1016/j.heliyon.2022.e12316 |
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author | Leija-Martínez, José J. Giacoman-Martínez, Abraham Del-Río-Navarro, Blanca E. Sanchéz-Muñoz, Fausto Hernández-Diazcouder, Adrián Muñoz-Hernández, Onofre Romero-Nava, Rodrigo Villafaña, Santiago Marchat, Laurence A. Hong, Enrique Huang, Fengyang |
author_facet | Leija-Martínez, José J. Giacoman-Martínez, Abraham Del-Río-Navarro, Blanca E. Sanchéz-Muñoz, Fausto Hernández-Diazcouder, Adrián Muñoz-Hernández, Onofre Romero-Nava, Rodrigo Villafaña, Santiago Marchat, Laurence A. Hong, Enrique Huang, Fengyang |
author_sort | Leija-Martínez, José J. |
collection | PubMed |
description | A higher Th17-immune response characterises obesity and obesity-related asthma phenotype. Nevertheless, obesity-related asthma has a more significant Th17-immune response than obesity alone. Retinoid-related orphan receptor C (RORC) is the essential transcription factor for Th17 polarisation. Previous studies have found that adolescents with obesity-related asthma presented upregulation of RORC, IL17A, and TNFA. However, the mechanisms that cause these higher mRNA expression levels in this asthmatic phenotype are poorly understood. Methylation directly regulates gene expression by adding a methyl group to carbon 5 of dinucleotide CpG cytosine. Thus, we evaluated the relationship between RORC, IL17A, and TNFA methylation status and mRNA expression levels to investigate a possible epigenetic regulation. A total of 102 adolescents (11–18 years) were studied in the following four groups: 1) healthy participants (HP), 2) allergic asthmatic participants (AAP), 3) obese participants without asthma (OP), and 4) non-allergic obesity-related asthma participants (OAP). Real-time qPCR assessed the methylation status and gene expression levels in peripheral blood leukocytes. Remarkably, the OAP and AAP groups have lower promoter methylation patterns of RORC, IL17A, and TNFA than the HP group. Notably, the OAP group presents lower RORC promoter methylation status than the OP group. Interestingly, RORC promoter methylation status was moderately negatively associated with gene expression of RORC (r(s) = −0.39, p < 0.001) and IL17A (r(s) = −0.37, p < 0.01), respectively. Similarly, the promoter methylation pattern of IL17A was moderately negatively correlated with IL17A gene expression (r(s) = −0.3, p < 0.01). There is also a moderate inverse relationship between TNFA promoter methylation status and TNFA gene expression (r(s) = −0.3, p < 0.01). The present study suggests an association between lower RORC, IL17A, and TNFA gene promoter methylation status with obesity-related asthma and allergic asthma. RORC, IL17A, and TNFA gene promoter methylation patterns are moderately inversely correlated with their respective mRNA expression levels. Therefore, DNA methylation may regulate RORC, IL17A, and TNF gene expression in both asthmatic phenotypes. |
format | Online Article Text |
id | pubmed-9798174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-97981742022-12-30 Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma Leija-Martínez, José J. Giacoman-Martínez, Abraham Del-Río-Navarro, Blanca E. Sanchéz-Muñoz, Fausto Hernández-Diazcouder, Adrián Muñoz-Hernández, Onofre Romero-Nava, Rodrigo Villafaña, Santiago Marchat, Laurence A. Hong, Enrique Huang, Fengyang Heliyon Research Article A higher Th17-immune response characterises obesity and obesity-related asthma phenotype. Nevertheless, obesity-related asthma has a more significant Th17-immune response than obesity alone. Retinoid-related orphan receptor C (RORC) is the essential transcription factor for Th17 polarisation. Previous studies have found that adolescents with obesity-related asthma presented upregulation of RORC, IL17A, and TNFA. However, the mechanisms that cause these higher mRNA expression levels in this asthmatic phenotype are poorly understood. Methylation directly regulates gene expression by adding a methyl group to carbon 5 of dinucleotide CpG cytosine. Thus, we evaluated the relationship between RORC, IL17A, and TNFA methylation status and mRNA expression levels to investigate a possible epigenetic regulation. A total of 102 adolescents (11–18 years) were studied in the following four groups: 1) healthy participants (HP), 2) allergic asthmatic participants (AAP), 3) obese participants without asthma (OP), and 4) non-allergic obesity-related asthma participants (OAP). Real-time qPCR assessed the methylation status and gene expression levels in peripheral blood leukocytes. Remarkably, the OAP and AAP groups have lower promoter methylation patterns of RORC, IL17A, and TNFA than the HP group. Notably, the OAP group presents lower RORC promoter methylation status than the OP group. Interestingly, RORC promoter methylation status was moderately negatively associated with gene expression of RORC (r(s) = −0.39, p < 0.001) and IL17A (r(s) = −0.37, p < 0.01), respectively. Similarly, the promoter methylation pattern of IL17A was moderately negatively correlated with IL17A gene expression (r(s) = −0.3, p < 0.01). There is also a moderate inverse relationship between TNFA promoter methylation status and TNFA gene expression (r(s) = −0.3, p < 0.01). The present study suggests an association between lower RORC, IL17A, and TNFA gene promoter methylation status with obesity-related asthma and allergic asthma. RORC, IL17A, and TNFA gene promoter methylation patterns are moderately inversely correlated with their respective mRNA expression levels. Therefore, DNA methylation may regulate RORC, IL17A, and TNF gene expression in both asthmatic phenotypes. Elsevier 2022-12-17 /pmc/articles/PMC9798174/ /pubmed/36590520 http://dx.doi.org/10.1016/j.heliyon.2022.e12316 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Leija-Martínez, José J. Giacoman-Martínez, Abraham Del-Río-Navarro, Blanca E. Sanchéz-Muñoz, Fausto Hernández-Diazcouder, Adrián Muñoz-Hernández, Onofre Romero-Nava, Rodrigo Villafaña, Santiago Marchat, Laurence A. Hong, Enrique Huang, Fengyang Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma |
title | Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma |
title_full | Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma |
title_fullStr | Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma |
title_full_unstemmed | Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma |
title_short | Promoter methylation status of RORC, IL17A, and TNFA in peripheral blood leukocytes in adolescents with obesity-related asthma |
title_sort | promoter methylation status of rorc, il17a, and tnfa in peripheral blood leukocytes in adolescents with obesity-related asthma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9798174/ https://www.ncbi.nlm.nih.gov/pubmed/36590520 http://dx.doi.org/10.1016/j.heliyon.2022.e12316 |
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