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Polymorphisms within the TNFSF4 and MAPKAPK2 Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium
Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascer...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823601/ https://www.ncbi.nlm.nih.gov/pubmed/33374839 http://dx.doi.org/10.3390/jof7010004 |
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author | Sánchez-Maldonado, Jose Manuel Moñiz-Díez, Ana ter Horst, Rob Campa, Daniele Cabrera-Serrano, Antonio José Martínez-Bueno, Manuel Garrido-Collado, María del Pilar Hernández-Mohedo, Francisca Fernández-Puerta, Laura López-Nevot, Miguel Ángel Cunha, Cristina González-Sierra, Pedro Antonio Springer, Jan Lackner, Michaela Alcazar-Fuoli, Laura Fianchi, Luana Aguado, José María Pagano, Livio López-Fernández, Elisa Clavero, Esther Potenza, Leonardo Luppi, Mario Moratalla, Lucia Solano, Carlos Sampedro, Antonio Cuenca-Estrella, Manuel Lass-Flörl, Cornelia Canzian, Federico Loeffler, Juergen Li, Yang Einsele, Hermann Netea, Mihai G. Vázquez, Lourdes Carvalho, Agostinho Jurado, Manuel Sainz, Juan |
author_facet | Sánchez-Maldonado, Jose Manuel Moñiz-Díez, Ana ter Horst, Rob Campa, Daniele Cabrera-Serrano, Antonio José Martínez-Bueno, Manuel Garrido-Collado, María del Pilar Hernández-Mohedo, Francisca Fernández-Puerta, Laura López-Nevot, Miguel Ángel Cunha, Cristina González-Sierra, Pedro Antonio Springer, Jan Lackner, Michaela Alcazar-Fuoli, Laura Fianchi, Luana Aguado, José María Pagano, Livio López-Fernández, Elisa Clavero, Esther Potenza, Leonardo Luppi, Mario Moratalla, Lucia Solano, Carlos Sampedro, Antonio Cuenca-Estrella, Manuel Lass-Flörl, Cornelia Canzian, Federico Loeffler, Juergen Li, Yang Einsele, Hermann Netea, Mihai G. Vázquez, Lourdes Carvalho, Agostinho Jurado, Manuel Sainz, Juan |
author_sort | Sánchez-Maldonado, Jose Manuel |
collection | PubMed |
description | Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4(rs7526628T/T) genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4(rs7526628T) allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungicidal activity (p = 0.048). In addition, we observed that each copy of the MAPKAPK2(rs12137965G) allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2(rs17013271T) allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2(rs12137965G) allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (p = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (p = 0.00097). Finally, we also found that carriers of the protective MAPKAPK2(rs17013271T) allele had decreased numbers of CD27-IgM-IgD- B cells (p = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (p = 0.00018 and 0.00023). Altogether, these results suggest a role of the TNFSF4 and MAPKAPK2 genes in determining IA risk. |
format | Online Article Text |
id | pubmed-7823601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78236012021-01-24 Polymorphisms within the TNFSF4 and MAPKAPK2 Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium Sánchez-Maldonado, Jose Manuel Moñiz-Díez, Ana ter Horst, Rob Campa, Daniele Cabrera-Serrano, Antonio José Martínez-Bueno, Manuel Garrido-Collado, María del Pilar Hernández-Mohedo, Francisca Fernández-Puerta, Laura López-Nevot, Miguel Ángel Cunha, Cristina González-Sierra, Pedro Antonio Springer, Jan Lackner, Michaela Alcazar-Fuoli, Laura Fianchi, Luana Aguado, José María Pagano, Livio López-Fernández, Elisa Clavero, Esther Potenza, Leonardo Luppi, Mario Moratalla, Lucia Solano, Carlos Sampedro, Antonio Cuenca-Estrella, Manuel Lass-Flörl, Cornelia Canzian, Federico Loeffler, Juergen Li, Yang Einsele, Hermann Netea, Mihai G. Vázquez, Lourdes Carvalho, Agostinho Jurado, Manuel Sainz, Juan J Fungi (Basel) Article Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4(rs7526628T/T) genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4(rs7526628T) allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungicidal activity (p = 0.048). In addition, we observed that each copy of the MAPKAPK2(rs12137965G) allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2(rs17013271T) allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2(rs12137965G) allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (p = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (p = 0.00097). Finally, we also found that carriers of the protective MAPKAPK2(rs17013271T) allele had decreased numbers of CD27-IgM-IgD- B cells (p = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (p = 0.00018 and 0.00023). Altogether, these results suggest a role of the TNFSF4 and MAPKAPK2 genes in determining IA risk. MDPI 2020-12-23 /pmc/articles/PMC7823601/ /pubmed/33374839 http://dx.doi.org/10.3390/jof7010004 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sánchez-Maldonado, Jose Manuel Moñiz-Díez, Ana ter Horst, Rob Campa, Daniele Cabrera-Serrano, Antonio José Martínez-Bueno, Manuel Garrido-Collado, María del Pilar Hernández-Mohedo, Francisca Fernández-Puerta, Laura López-Nevot, Miguel Ángel Cunha, Cristina González-Sierra, Pedro Antonio Springer, Jan Lackner, Michaela Alcazar-Fuoli, Laura Fianchi, Luana Aguado, José María Pagano, Livio López-Fernández, Elisa Clavero, Esther Potenza, Leonardo Luppi, Mario Moratalla, Lucia Solano, Carlos Sampedro, Antonio Cuenca-Estrella, Manuel Lass-Flörl, Cornelia Canzian, Federico Loeffler, Juergen Li, Yang Einsele, Hermann Netea, Mihai G. Vázquez, Lourdes Carvalho, Agostinho Jurado, Manuel Sainz, Juan Polymorphisms within the TNFSF4 and MAPKAPK2 Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium |
title | Polymorphisms within the TNFSF4 and MAPKAPK2 Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium |
title_full | Polymorphisms within the TNFSF4 and MAPKAPK2 Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium |
title_fullStr | Polymorphisms within the TNFSF4 and MAPKAPK2 Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium |
title_full_unstemmed | Polymorphisms within the TNFSF4 and MAPKAPK2 Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium |
title_short | Polymorphisms within the TNFSF4 and MAPKAPK2 Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium |
title_sort | polymorphisms within the tnfsf4 and mapkapk2 loci influence the risk of developing invasive aspergillosis: a two-stage case control study in the context of the aspbiomics consortium |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823601/ https://www.ncbi.nlm.nih.gov/pubmed/33374839 http://dx.doi.org/10.3390/jof7010004 |
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