AUTHOR=Lupiañez Carmen B. , Villaescusa María T. , Carvalho Agostinho , Springer Jan , Lackner Michaela , Sánchez-Maldonado José M. , Canet Luz M. , Cunha Cristina , Segura-Catena Juana , Alcazar-Fuoli Laura , Solano Carlos , Fianchi Luana , Pagano Livio , Potenza Leonardo , Aguado José M. , Luppi Mario , Cuenca-Estrella Manuel , Lass-Flörl Cornelia , Einsele Hermann , Vázquez Lourdes ,  PCRAGA Study Group , Ríos-Tamayo Rafael , Loeffler Jurgen , Jurado Manuel , Sainz Juan 

TITLE=Common Genetic Polymorphisms within NFκB-Related Genes and the Risk of Developing Invasive Aspergillosis

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.01243

DOI=10.3389/fmicb.2016.01243

ISSN=1664-302X

ABSTRACT=<p>Invasive Aspergillosis (IA) is an opportunistic infection caused by <italic>Aspergillus</italic>, 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 <italic>NF</italic>κ<italic>B1, NF</italic>κ<italic>B2, RelA, RelB, Rel</italic>, and <italic>IRF4</italic> 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 <italic>IRF4</italic><sub>rs12203592T/T</sub> genotype had a six-fold increased risk of developing the infection when compared with those carrying the C allele (OR<sub>REC</sub> = 6.24, 95%CI 1.25–31.2, <italic>P</italic> = 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 IRF4<sub>AAT<underline>C</underline></sub> and IRF4<sub>GGT<underline>C</underline></sub> haplotypes (not including the <italic>IRF4</italic><sub>rs12203592T</sub> 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 <italic>IRF4</italic><sub>rs12203592</sub> 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.</p>