common genetic polymorphisms within nfκb-related genes and the risk of developing invasive aspergillosis
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2016
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Abstract
Invasive Aspergillosis (IA) is an opportunistic infection caused by Aspergillus, a ubiquitously present airborne pathogenic mould. 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 6-fold increased risk of developing the infection when compared with those carrying the C allele (OR-Rec=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.
| Reference Key |
lupiaez2016frontierscommon
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| Authors | ;Carmen Belén Lupiañez;Carmen Belén Lupiañez;María Teresa Villaescusa;María Teresa Villaescusa;Agostinho Carvalho;Agostinho Carvalho;Jan Springer;Michaela Lackner;José Manuel Sánchez-Maldonado;Luz María Canet;Cristina Cunha;Juana Segura-Catena;Juana Segura-Catena;Laura Alcazar-Fuoli;Carlos Solano;Luana Fianchi;Livio Pagano;Leonardo Potenza;José María Aguado;Mario Luppi;Manuel Cuenca-Estrella;Cornelia Lass-Flörl;Hermann Einsele;Lourdes Vázquez;PCRAGA Study Group;Rafael Ríos-Tamayo;Rafael Ríos-Tamayo;Jurgen Loeffler;Manuel Jurado;Manuel Jurado;Juan Sainz;Juan Sainz |
| Journal | journal of magnetic resonance (san diego, calif : 1997) |
| Year | 2016 |
| DOI |
10.3389/fmicb.2016.01243
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