TY  - JOUR
A1  - Lupiañez, Carmen B.
A1  - Villaescusa, Maria T.
A1  - Carvalho, Agostinho
A1  - Springer, Jan
A1  - Lackner, Michaela
A1  - Sánchez-Maldonado, José M.
A1  - Canet, Luz M.
A1  - Cunha, Cristina
A1  - Segura-Catena, Joana
A1  - Alcazar-Fuoli, Laura
A1  - Solano, Carlos
A1  - Fianchi, Luana
A1  - Pagano, Livio
A1  - Potenza, Leonardo
A1  - Aguado, José M.
A1  - Luppi, Mario
A1  - Cuenca-Estrella, Manuel
A1  - Lass-Flörl, Cornelia
A1  - Einsele, Hermann
A1  - Vázquez, Lourdes
A1  - Ríos-Tamayo, Rafael
A1  - Loeffler, Jürgen
A1  - Jurado, Manuel
A1  - Sainz, Juan
T1  - Common Genetic Polymorphisms within NF kappa B-Related Genes and the Risk of Developing Invasive Aspergillosis
JF  - Frontiers in Microbiology
N2  - Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mold. A growing number of studies suggest a major host genetic component in disease susceptibility. Here, we evaluated whether 14 single-nucleotide polymorphisms within NFκB1, NFκB2, RelA, RelB, Rel, and IRF4 genes influence the risk of IA in a population of 834 high-risk patients (157 IA and 677 non-IA) recruited through a collaborative effort involving the aspBIOmics consortium and four European clinical institutions. No significant overall associations between selected SNPs and the risk of IA were found in this large cohort. Although a hematopoietic stem cell transplantation (HSCT)-stratified analysis revealed that carriers of the IRF4rs12203592T/T genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (ORREC = 6.24, 95%CI 1.25–31.2, P = 0.026), the association of this variant with IA risk did not reach significance at experiment-wide significant threshold. In addition, we found an association of the IRF4AATC and IRF4GGTC haplotypes (not including the IRF4rs12203592T risk allele) with a decreased risk of IA but the magnitude of the association was similar to the one observed in the single-SNP analysis, which indicated that the haplotypic effect on IA risk was likely due to the IRF4rs12203592 SNP. Finally, no evidence of significant interactions among the genetic markers tested and the risk of IA was found. These results suggest that the SNPs on the studied genes do not have a clinically relevant impact on the risk of developing IA.
KW  - Invasive Aspergillosis
KW  - genetic polymorphisms
KW  - susceptibility
KW  - NFkB-relatedgenes
KW  - interaction
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165209
VL  - 7
IS  - 1243
ER  - 
TY  - JOUR
A1  - Averdunk, Luisa
A1  - Bernhagen, Jürgen
A1  - Fehnle, Karl
A1  - Surowy, Harald
A1  - Lüdecke, Hermann-Josef
A1  - Mucha, Sören
A1  - Meybohm, Patrick
A1  - Wieczorek, Dagmar
A1  - Leng, Lin
A1  - Marx, Gernot
A1  - Leaf, David E.
A1  - Zarbock, Alexander
A1  - Zacharowski, Kai
A1  - Bucala, Richard
A1  - Stoppe, Christian
T1  - The Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms (rs3063368, rs755622) predict acute kidney injury and death after cardiac surgery
JF  - Journal of Clinical Medicine
N2  - Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT\(_{5–7}\) (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT\(_7\)) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT\(_7\) were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT\(_7\) predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT\(_7\) was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT\(_7\) allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.
KW  - acute kidney injury
KW  - genetic polymorphisms
KW  - risk prediction
KW  - (cardiac) surgery
KW  - inflammatory cytokines
KW  - clinical studies
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213126
SN  - 2077-0383
VL  - 9
IS  - 9
ER  -