@misc{10481/66587,
year = {2020},
url = {http://hdl.handle.net/10481/66587},
abstract = {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 twostage 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.},
organization = {Instituto de Salud Carlos III

PI17/02276},
organization = {ERA-NET PathoGenoMics 	
PIM2010EPA-00756
0315900A},
organization = {Collaborative Research Center/Transregio 124 FungiNet},
organization = {Portuguese Foundation for Science and Technology

PTDC/SAU-SER/29635/2017
PTDC/MED-GEN/28778/2017
CEECIND/03628/2017
CEECIND/04058/2018},
organization = {European Union (EU)

847507},
organization = {La Caixa Foundation

ID 100010434},
organization = {Portuguese Foundation for Science and Technology

LCF/PR/HP17/52190003},
organization = {PI20/01845},
organization = {PI12/02688},
publisher = {MDPI},
keywords = {Invasive aspergillosis},
keywords = {TNFSF4},
keywords = {MAPKAPK2},
keywords = {Genetic susceptibility},
keywords = {B cells},
keywords = {Monocytes},
keywords = {Serum biomarkers},
keywords = {TSLP},
keywords = {TNFSF14},
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},
doi = {10.3390/jof7010004},
author = {Sánchez Maldonado, José Manuel and Moñiz Díez, Ana and Cabrera Serrano, Antonio José and Martínez Bueno, Manuel and López Nevot, Miguel Ángel and Garrido Collado, María del Pilar and Hernández Mohedo, Francisca and Fernández Puerta, Laura and González Sierra, Pedro Antonio and Sáinz Pérez, Juan},
}