title: Genetic susceptibility to allergic bronchopulmonary aspergillosis in asthma: a genetic association study.
abstract: BACKGROUND
  In patients with asthma, the fungusAspergillus fumigatuscan cause allergic bronchopulmonary aspergillosis (ABPA). Familial ABPA is reported, and some genetic factors have been associated with the disease, however, these are small studies (n ≤ 38) and do not explain all cases of ABPA.
  
  
  METHODS
  We analysed SNPs in 95 ABPA patients, comparing frequencies to 152 atopic asthmatic and 279 healthy controls. Twenty two genes were selected from literature, and 195 tagging SNPs were analysed for genetic association with ABPA using logistic regression corrected for multiple testing. We also analysed monocyte-derived macrophage gene expression before and during co-culture withA. fumigatus.
  
  
  RESULTS
  Seventeen ABPA-associated SNPs (ABPA v Atopic asthma) were identified. Three remained significant after correction for multiple testing; IL13 rs20541, IL4R rs3024656, TLR3 rs1879026. We also identified minor differences in macrophage gene expression responses in the ABPA group compared to the control groups.
  
  
  CONCLUSIONS
  Multiple SNPs are now associated with ABPA. Some are novel associations. These associations implicate cytokine pathways and receptors in the aberrant response toA. fumigatusand susceptibility to ABPA, providing insights into the pathogenesis of ABPA and/or its complications. We hope these results will lead to increased understanding and improved treatment and diagnostics for ABPA.
authors.affiliation: Manchester Fungal Infection Group (MFIG), The University of Manchester, Manchester, UK ; Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Nicola L D
authors.initials: NL
authors.lastname: Overton
authors.affiliation: Manchester Fungal Infection Group (MFIG), The University of Manchester, Manchester, UK ; Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Denning
authors.affiliation: Manchester Fungal Infection Group (MFIG), The University of Manchester, Manchester, UK ; Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Bowyer
authors.affiliation: Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Simpson
keywords: ABPA; Asthma; Genetic susceptibility; IL13; IL4R; TLR3