Overton Nicola L D, Denning David W, Bowyer Paul, Simpson Angela
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.
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.
Allergy Asthma Clin Immunol. 2016 Sep 27;12:47. doi: 10.1186/s13223-016-0152-y. eCollection 2016.
In patients with asthma, the fungus can 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.
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 with .
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.
Multiple SNPs are now associated with ABPA. Some are novel associations. These associations implicate cytokine pathways and receptors in the aberrant response to and 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.
在哮喘患者中，真菌可引起变应性支气管肺曲霉病（ABPA）。有家族性ABPA的报道，且一些遗传因素与该病相关，然而，这些都是小型研究（n≤38），并未解释所有ABPA病例。
我们分析了95例ABPA患者的单核苷酸多态性（SNP），并将其频率与152例特应性哮喘患者及279例健康对照进行比较。从文献中选取22个基因，使用经多重检验校正的逻辑回归分析195个标签SNP与ABPA的遗传关联。我们还分析了单核细胞衍生巨噬细胞在与……共培养之前及期间的基因表达。
鉴定出17个与ABPA相关的SNP（ABPA与特应性哮喘比较）。经多重检验校正后，3个仍具有显著性；IL13 rs20541、IL4R rs3024656、TLR3 rs1879026。我们还发现ABPA组与对照组相比，巨噬细胞基因表达反应存在细微差异。
现在多个SNP与ABPA相关。其中一些是新的关联。这些关联表明细胞因子途径和受体在对……的异常反应及ABPA易感性中起作用，为ABPA的发病机制和/或其并发症提供了见解。我们希望这些结果将增进对ABPA的理解，并改善其治疗和诊断。
