title: Common Genetic Polymorphisms within NFκB-Related Genes and the Risk of Developing Invasive Aspergillosis.
abstract: 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.
authors: Genomic Oncology Area, GENYO, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS GranadaGranada, Spain; Hematology Department, Virgen de las Nieves University HospitalGranada, Spain.
authors: Carmen B
authors: CB
authors: Lupiañez
authors: Hematology Department, University Hospital of SalamancaSalamanca, Spain; Hematology Department, Jiménez Díaz FoundationMadrid, Spain.
authors: María T
authors: MT
authors: Villaescusa
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of MinhoBraga, Portugal; ICVS/3B's - PT Government Associate LaboratoryBraga, Portugal.
authors: Agostinho
authors: A
authors: Carvalho
authors: Universitätsklinikum Würzburg, Medizinische Klinik II Würzburg, Germany.
authors: Jan
authors: J
authors: Springer
authors: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck Innsbruck, Austria.
authors: Michaela
authors: M
authors: Lackner
authors: Genomic Oncology Area, GENYO, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada Granada, Spain.
authors: José M
authors: JM
authors: Sánchez-Maldonado
authors: Genomic Oncology Area, GENYO, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada Granada, Spain.
authors: Luz M
authors: LM
authors: Canet
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of MinhoBraga, Portugal; ICVS/3B's - PT Government Associate LaboratoryBraga, Portugal.
authors: Cristina
authors: C
authors: Cunha
authors: Genomic Oncology Area, GENYO, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS GranadaGranada, Spain; Hematology Department, Virgen de las Nieves University HospitalGranada, Spain.
authors: Juana
authors: J
authors: Segura-Catena
authors: Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III Madrid, Spain.
authors: Laura
authors: L
authors: Alcazar-Fuoli
authors: Hematology Department, Clinic University Hospital of Valencia Valencia, Spain.
authors: Carlos
authors: C
authors: Solano
authors: Istituto di Ematologia, Università Cattolica del S. Cuore Rome, Italy.
authors: Luana
authors: L
authors: Fianchi
authors: Istituto di Ematologia, Università Cattolica del S. Cuore Rome, Italy.
authors: Livio
authors: L
authors: Pagano
authors: Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia AOU Policlinico, Modena, Italy.
authors: Leonardo
authors: L
authors: Potenza
authors: Unit of Infectious Diseases, University Hospital 12 de Octubre, Research Institute of Hospital 12 de Octubre (i+12) Madrid, Spain.
authors: José M
authors: JM
authors: Aguado
authors: Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia AOU Policlinico, Modena, Italy.
authors: Mario
authors: M
authors: Luppi
authors: Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III Madrid, Spain.
authors: Manuel
authors: M
authors: Cuenca-Estrella
authors: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck Innsbruck, Austria.
authors: Cornelia
authors: C
authors: Lass-Flörl
authors: Universitätsklinikum Würzburg, Medizinische Klinik II Würzburg, Germany.
authors: Hermann
authors: H
authors: Einsele
authors: Hematology Department, University Hospital of Salamanca Salamanca, Spain.
authors: Lourdes
authors: L
authors: Vázquez
authors: Genomic Oncology Area, GENYO, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS GranadaGranada, Spain; Hematology Department, Virgen de las Nieves University HospitalGranada, Spain.
authors: Rafael
authors: R
authors: Ríos-Tamayo
authors: Universitätsklinikum Würzburg, Medizinische Klinik II Würzburg, Germany.
authors: Jurgen
authors: J
authors: Loeffler
authors: Genomic Oncology Area, GENYO, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS GranadaGranada, Spain; Hematology Department, Virgen de las Nieves University HospitalGranada, Spain.
authors: Manuel
authors: M
authors: Jurado
authors: Genomic Oncology Area, GENYO, Center for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS GranadaGranada, Spain; Hematology Department, Virgen de las Nieves University HospitalGranada, Spain.
authors: Juan
authors: J
authors: Sainz
keywords: Invasive Aspergillosis; NFκB-related genes; genetic polymorphisms; interaction; susceptibility