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Int J Immunogenet. 2017 Jun;44(3):93-106. doi: 10.1111/iji.12312. Epub 2017 Mar 31.

Genetic susceptibility to severe asthma with fungal sensitization.

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Division of Infection Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, The University of Manchester, Manchester, UK.
Manchester Fungal Infection Group (MFIG), The University of Manchester, Manchester, UK.


Severe asthma is problematic and its pathogenesis poorly understood. Fungal sensitization is common, and many patients with severe asthma with fungal sensitization (SAFS), used to denote this subgroup of asthma, respond to antifungal therapy. We have investigated 325 haplotype-tagging SNPs in 22 candidate genes previously associated with aspergillosis in patients with SAFS, with comparisons in atopic asthmatics and healthy control patients, of whom 47 SAFS, 279 healthy and 152 atopic asthmatic subjects were genotyped successfully. Significant associations with SAFS compared with atopic asthma included Toll-like receptor 3 (TLR3) (p = .009), TLR9 (p = .025), C-type lectin domain family seven member A (dectin-1) (p = .043), interleukin-10 (IL-10) (p = .0010), mannose-binding lectin (MBL2) (p = .007), CC-chemokine ligand 2 (CCL2) (2 SNPs, p = .025 and .041), CCL17 (p = .002), plasminogen (p = .049) and adenosine A2a receptor (p = .024). These associations differ from those found in ABPA in asthma, indicative of contrasting disease processes. Additional and broader genetic association studies in SAFS, combined with experimental work, are likely to contribute to our understanding of different phenotypes of problematic asthma.


allergy; asthma; disease association; disease association studies; genetics; polymorphism

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