Overton N L, Simpson A, Bowyer P, Denning D W
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.
Int J Immunogenet. 2017 Jun;44(3):93-106. doi: 10.1111/iji.12312. Epub 2017 Mar 31.
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.
重度哮喘问题重重，其发病机制仍知之甚少。真菌致敏现象常见，许多重度哮喘合并真菌致敏（SAFS）患者（此为哮喘的一个亚组）对抗真菌治疗有反应。我们在22个先前与SAFS患者曲霉病相关的候选基因中研究了325个单倍型标签单核苷酸多态性（SNP），并与特应性哮喘患者和健康对照患者进行比较，成功对其中47例SAFS患者、279例健康受试者和152例特应性哮喘受试者进行了基因分型。与特应性哮喘相比，SAFS的显著关联基因包括Toll样受体3（TLR3）（p = 0.009）、TLR9（p = 0.025）、C型凝集素结构域家族7成员A（dectin-1）（p = 0.043）、白细胞介素-10（IL-10）（p = 0.001）、甘露糖结合凝集素（MBL2）（p = 0.007）、CC趋化因子配体2（CCL2）（2个SNP，p = 0.025和0.041）、CCL17（p = 0.002）、纤溶酶原（p = 0.049）和腺苷A2a受体（p = 0.024）。这些关联与哮喘中变应性支气管肺曲霉病（ABPA）的关联不同，表明疾病过程存在差异。对SAFS进行更多更广泛的基因关联研究，并结合实验工作，可能有助于我们理解问题重重的哮喘的不同表型。
