Ascaris exposure and its association with lung function, asthma, and DNA methylation in Northern Europe - 03/06/22
, Negusse Kitaba, PhD e, Torgeir Storaas, MD, PhD d, Vivi Schlünssen, MD, PhD f, g, Kai Triebner, PhD a, b, John W. Holloway, PhD e, William G.C. Horsnell, PhD h, i, j, ⁎ , Cecilie Svanes, MD, PhD d, c, Randi J. Bertelsen, PhD a, kAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Ascaris, helminth, lung function, asthma, EWAS, DNA methylation, RHINESSA
Abbreviations used : aOR, CpG, dmCpG, DMR, EWAS, HDM, NTU, RHINESSA, SPT
Plan
| The last 3 authors contributed equally to this article, and all should be considered senior author. |
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| 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. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 149 - N° 6
P. 1960-1969 - juin 2022 Retour au numéro
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