Ascaris exposure and its association with lung function, asthma, and DNA methylation in Northern Europe

Nils O Jõgi, Negusse Kitaba, Torgeir Storaas, Vivi Schlünssen, Kai Triebner, John W Holloway, William G C Horsnell, Cecilie Svanes, Randi J Bertelsen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume2022
Early online date4 Jan 2022
DOIs
Publication statusE-pub ahead of print - 4 Jan 2022

Keywords

  • Ascaris
  • helminth
  • lung function
  • asthma
  • EWAS
  • DNA methylation
  • RHINESSA

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