Polymorphisms within the and Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium.
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Authors
ánchez-Maldonado, Jose ManuelMoñiz-Díez, Ana
Rob Ter Horst, Daniele Campa
Cabrera-Serrano, Antonio José
Garrido-Collado, María Del Pilar
Hernández-Mohedo, Fracisca
Fernández-Puerta, Laura
López-Nevot, , Miguel Ángel
Cunha, Ctistina
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
Pcraga Study Group
Canzian, Federico
Loeffler, Juergen
Li, Yang
Einsele, Hermann
Netea, Mihai G.
Vázquez, Lourdes
Carvalho, Agostinho
Jurado, Manuel
Sainz, Juan
Issue Date
2020-12-23
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Show full item recordAbstract
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 TNFSF4rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4rs7526628T 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 MAPKAPK2rs12137965G allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2rs17013271T allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2rs12137965G 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 MAPKAPK2rs17013271T 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.Citation
. J Fungi (Basel). 2020 Dec 23;7(1):E4. doi: 10.3390/jof7010004.Affiliation
CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.Publisher
MDPIPubMed ID
33374839Type
ArticleLanguage
enEISSN
2309-608Xae974a485f413a2113503eed53cd6c53
10.3390/jof7010004
Scopus Count
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- Creative Commons
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