Genetic susceptibility to allergic bronchopulmonary aspergillosis in asthma: a genetic association study
Nicola L D Overton1, David W Denning1, Paul Bowyer1
1Manchester 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.
Background:
In patients with asthma, the fungus Aspergillus fumigatus 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.
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 with A. 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 to A. fumigatus 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.
Insights
Genetic factors influence allergic bronchopulmonary aspergillosis (ABPA). This study identified novel single nucleotide polymorphisms (SNPs) associated with ABPA, implicating cytokine pathways in disease susceptibility.
Area of Science:
- Immunogenetics
- Pulmonology
- Mycology
Background:
- Allergic bronchopulmonary aspergillosis (ABPA) is an asthma complication caused by Aspergillus fumigatus.
- While familial ABPA suggests genetic links, previous studies were small and insufficient to explain all cases.
Purpose of the Study:
- To investigate genetic associations with ABPA.
- To explore the role of specific genes and macrophage responses in ABPA pathogenesis.
Main Methods:
- Analyzed single nucleotide polymorphisms (SNPs) in 95 ABPA patients, 152 atopic asthmatics, and 279 healthy controls.
- Examined 195 tagging SNPs across 22 selected genes for association with ABPA using logistic regression.
- Assessed monocyte-derived macrophage gene expression during co-culture with Aspergillus fumigatus.
Main Results:
- Identified 17 SNPs associated with ABPA compared to atopic asthma.
- Three SNPs (IL13 rs20541, IL4R rs3024656, TLR3 rs1879026) remained significant after multiple testing correction.
- Observed subtle differences in macrophage gene expression between ABPA patients and controls.
Conclusions:
- Multiple SNPs, including novel associations, are linked to ABPA susceptibility.
- These findings highlight the involvement of cytokine pathways and receptors in the immune response to Aspergillus fumigatus.
- Results offer insights into ABPA pathogenesis, potentially improving future diagnostics and treatments.
More Related Videos
Related Concept Videos
01:20Asthma: Pathogenesis and Management
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
01:26Asthma-II: Pathophysiology and Classification
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
01:29Asthma-I: Introduction
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation
01:30Asthma-IV: Diagnostic and Management
Clinical Assessment for Asthma:
This is the first step in diagnosing and managing asthma. It includes:
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...