Ascaris exposure and its association with lung function, asthma, and DNA methylation in Northern Europe
Ascaris exposure and its association with lung function, asthma, and DNA methylation in Northern Europe
Background
Ascaris infections, with a worldwide prevalence above 10%, can cause respiratory pathology. However, long-term effects on lung function in humans are largely unknown.
Objective
We investigated the associations of Ascaris exposure with lung function, asthma, and DNA methylation.
Methods
Serum Ascaris IgG antibodies were measured in 671 adults aged 18 to 47 years (46% women) from Aarhus, Bergen, and Tartu RHINESSA study centers. Seropositivity was defined as IgG above the 90th percentile. Linear and logistic regressions were used to analyze Ascaris seropositivity as associated with lung function and asthma, adjusted for age, height, and smoking and clustered by center. DNA methylation in blood was profiled by a commercial methylation assay.
Results
Ascaris seropositivity was associated with lower FEV1 (−247 mL; 95% CI, −460, −34) and higher odds for asthma (adjusted odds ratio, 5.84; 95% CI, 1.67, 20.37) among men but not women, also after further adjusting for house dust mite sensitivity, consistent across study centers. At a genome-wide level, Ascaris exposure was associated with 23 differentially methylated sites in men and 3 in women. We identified hypermethylation of the MYBPC1 gene, which can regulate airway muscle contraction. We also identified genes linked to asthma pathogenesis such as CRHR1 and GRK1, as well as a differentially methylated region in the PRSS22 gene linked to nematode infection.
Conclusion
Ascaris exposure was associated with substantially lower lung function and increased asthma risk among men. Seropositive participants had sex-specific differences in DNA methylation compared to the unexposed, thus suggesting that exposure may lead to sex-specific epigenetic changes associated with lung pathology.
Ascaris, DNA methylation, EWAS, RHINESSA, asthma, helminth, lung function
1960-1969
Jõgi, Nils O.
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Kitaba, Negusse
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Storaas, Torgeir
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Schlünssen, Vivi
872b391d-a114-4392-9701-265792601c79
Triebner, Kai
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Holloway, John W.
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Horsnell, William G.c.
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Svanes, Cecilie
4a547f80-e3d3-47b4-ae0a-2741ad93c629
Bertelsen, Randi J.
b3f942fa-f7a5-4b26-a2c2-2d1d1b50e115
1 June 2022
Jõgi, Nils O.
bce12b83-b4fd-4cf0-9606-de40882df877
Kitaba, Negusse
5e35ae4a-edaa-4b78-bcb6-00628c3b6e83
Storaas, Torgeir
93c1ed64-130e-4902-bcd6-5e359ed1e4c4
Schlünssen, Vivi
872b391d-a114-4392-9701-265792601c79
Triebner, Kai
5b48a3c1-e91b-424d-9abc-459d4a25c44c
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Horsnell, William G.c.
b490aa17-3f96-49d3-8b02-821bf14e2537
Svanes, Cecilie
4a547f80-e3d3-47b4-ae0a-2741ad93c629
Bertelsen, Randi J.
b3f942fa-f7a5-4b26-a2c2-2d1d1b50e115
Jõgi, Nils O., Kitaba, Negusse, Storaas, Torgeir, Schlünssen, Vivi, Triebner, Kai, Holloway, John W., Horsnell, William G.c., Svanes, Cecilie and Bertelsen, Randi J.
(2022)
Ascaris exposure and its association with lung function, asthma, and DNA methylation in Northern Europe.
Journal of Allergy and Clinical Immunology, 149 (6), .
(doi:10.1016/j.jaci.2021.11.013).
Abstract
Background
Ascaris infections, with a worldwide prevalence above 10%, can cause respiratory pathology. However, long-term effects on lung function in humans are largely unknown.
Objective
We investigated the associations of Ascaris exposure with lung function, asthma, and DNA methylation.
Methods
Serum Ascaris IgG antibodies were measured in 671 adults aged 18 to 47 years (46% women) from Aarhus, Bergen, and Tartu RHINESSA study centers. Seropositivity was defined as IgG above the 90th percentile. Linear and logistic regressions were used to analyze Ascaris seropositivity as associated with lung function and asthma, adjusted for age, height, and smoking and clustered by center. DNA methylation in blood was profiled by a commercial methylation assay.
Results
Ascaris seropositivity was associated with lower FEV1 (−247 mL; 95% CI, −460, −34) and higher odds for asthma (adjusted odds ratio, 5.84; 95% CI, 1.67, 20.37) among men but not women, also after further adjusting for house dust mite sensitivity, consistent across study centers. At a genome-wide level, Ascaris exposure was associated with 23 differentially methylated sites in men and 3 in women. We identified hypermethylation of the MYBPC1 gene, which can regulate airway muscle contraction. We also identified genes linked to asthma pathogenesis such as CRHR1 and GRK1, as well as a differentially methylated region in the PRSS22 gene linked to nematode infection.
Conclusion
Ascaris exposure was associated with substantially lower lung function and increased asthma risk among men. Seropositive participants had sex-specific differences in DNA methylation compared to the unexposed, thus suggesting that exposure may lead to sex-specific epigenetic changes associated with lung pathology.
Text
PIIS0091674921017978[70]
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More information
Accepted/In Press date: 5 November 2021
e-pub ahead of print date: 4 January 2022
Published date: 1 June 2022
Additional Information:
Funding Information:
The RHINESSA study received funding from the Research Council of Norway (grants 274767, 214123, 228174, 230827 , and 273838 ), European Research Council Starting Grant project BRuSH 804199, the European Union’s Horizon 2020 research and innovation program (grant 633212 , Ageing Lungs in European Cohorts Study WP2), the Bergen Medical Research Foundation , and the Western Norwegian Regional Health Authorities (grants 912011, 911892 , and 911631 ). In addition, study centers received local funding from the following: for Bergen, the above grants for study establishment and coordination, as well as the World University Network (Research Development Fund and Sustainability Fund grants), the Norwegian Labour Inspection, and the Norwegian Asthma and Allergy Association; for Tartu, the Estonian Research Council (grant PUT562); and for Aarhus, the Danish Wood Foundation (grant 444508795) and the Danish Working Environment Authority (grant 20150067134). N. O. Jõgi was funded by a Department of Clinical Science PhD grant from the University of Bergen.
Funding Information:
The RHINESSA study received funding from the Research Council of Norway (grants 274767, 214123, 228174, 230827, and 273838), European Research Council Starting Grant project BRuSH 804199, the European Union's Horizon 2020 research and innovation program (grant 633212, Ageing Lungs in European Cohorts Study WP2), the Bergen Medical Research Foundation, and the Western Norwegian Regional Health Authorities (grants 912011, 911892, and 911631). In addition, study centers received local funding from the following: for Bergen, the above grants for study establishment and coordination, as well as the World University Network (Research Development Fund and Sustainability Fund grants), the Norwegian Labour Inspection, and the Norwegian Asthma and Allergy Association; for Tartu, the Estonian Research Council (grant PUT562); and for Aarhus, the Danish Wood Foundation (grant 444508795) and the Danish Working Environment Authority (grant 20150067134). N. O. Jõgi was funded by a Department of Clinical Science PhD grant from the University of Bergen.
Publisher Copyright:
Copyright © 1969, Elsevier
Keywords:
Ascaris, DNA methylation, EWAS, RHINESSA, asthma, helminth, lung function
Identifiers
Local EPrints ID: 454354
URI: http://eprints.soton.ac.uk/id/eprint/454354
ISSN: 0091-6749
PURE UUID: 4ccf73c1-ebb6-475d-ab5c-3a7cbaa0d9c8
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Date deposited: 08 Feb 2022 17:33
Last modified: 17 Mar 2024 07:03
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Contributors
Author:
Nils O. Jõgi
Author:
Torgeir Storaas
Author:
Vivi Schlünssen
Author:
Kai Triebner
Author:
William G.c. Horsnell
Author:
Cecilie Svanes
Author:
Randi J. Bertelsen
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