Lupiañez, Carmen BVillaescusa, María TCarvalho, AgostinhoSpringer, JanLackner, MichaelaSánchez-Maldonado, José MCanet, Luz MCunha, CristinaSegura-Catena, JuanaAlcazar-Fuoli, LauraSolano, CarlosFianchi, LuanaPagano, LivioPotenza, LeonardoAguado, José MLuppi, MarioCuenca-Estrella, ManuelLass-Flörl, CorneliaEinsele, HermannVázquez, LourdesRíos-Tamayo, RafaelLoeffler, JurgenJurado, ManuelSainz, Juan2016-11-242016-11-242016-08-12Lupiañez CB, Villaescusa MT, Carvalho A, Springer J, Lackner M, Sánchez-Maldonado JM, et al. Common Genetic Polymorphisms within NFκB-Related Genes and the Risk of Developing Invasive Aspergillosis. Front Microbiol. 2016; 7:1243http://hdl.handle.net/10668/2541Journal Article;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 IRF4 rs12203592T/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 IRF4 rs12203592T 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 IRF4 rs12203592 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.enAspergilosisSusceptibilidad a enfermedadesMarcadores genéticosGenotipoHaplotiposTrasplante de células madre hematopoyéticasHumanosNucleótidosInfecciones oportunistasPolimorfismo de nucleótido simpleMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Mycoses::Hyalohyphomycosis::AspergillosisMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease SusceptibilityMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype::Genetic MarkersMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::HaplotypesMedical Subject Headings::Organisms::Eukaryota::Fungi::Mitosporic Fungi::AspergillusMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Hematopoietic Stem Cell TransplantationMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Glycosides::NucleotidesMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Infection::Opportunistic InfectionsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotideresearch article27570521open access10.3389/fmicb.2016.012431664-302XPMC4982195