Publication: 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.
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Identifiers
Date
2020-12-23
Authors
Sanchez-Maldonado, Jose Manuel
Moñiz-Diez, Ana
Ter Horst, Rob
Campa, Daniele
Cabrera-Serrano, Antonio Jose
Martinez-Bueno, Manuel
Garrido-Collado, Maria Del Pilar
Hernandez-Mohedo, Francisca
Fernandez-Puerta, Laura
Lopez-Nevot, Miguel Angel
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI AG
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 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.
Description
MeSH Terms
Humans
Polymorphism, Single Nucleotide
Thymic Stromal Lymphopoietin
Tumor Necrosis Factor Ligand Superfamily Member 14
MAP-kinase-activated kinase 2
Alleles
Polymorphism, Single Nucleotide
Thymic Stromal Lymphopoietin
Tumor Necrosis Factor Ligand Superfamily Member 14
MAP-kinase-activated kinase 2
Alleles
DeCS Terms
Alelos
Fosfotransferasas
Humanos
Linfopoyetina del estroma tímico
Miembro 14 de la Superfamilia de ligandos de factores de necrosis
Tumoral
Polimorfismo de nucleótido simple
Fosfotransferasas
Humanos
Linfopoyetina del estroma tímico
Miembro 14 de la Superfamilia de ligandos de factores de necrosis
Tumoral
Polimorfismo de nucleótido simple
CIE Terms
Keywords
B cells, MAPKAPK2, TNFSF14, TNFSF4, TSLP, genetic susceptibility, invasive aspergillosis, monocytes, serum biomarkers
Citation
Sánchez-Maldonado JM, Moñiz-Díez A, Ter Horst R, Campa D, Cabrera-Serrano AJ, Martínez-Bueno M, et al. 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. J Fungi (Basel). 2020 Dec 23;7(1):4.