TOLLIP and MUC5B modulate the effect of ambient NO2 on respiratory symptoms in infancy.

Gorlanova, Olga; Rüttimann, Céline; Soti, Andras; de Hoogh, Kees; Vienneau, Danielle; Künstle, Noëmi; Da Silva Sena, Carla Rebeca; Steinberg, Ruth; Bovermann, Xenia; Schulzke, Sven; Latzin, Philipp; Röösli, Martin; Frey, Urs; Müller, Loretta (2024). TOLLIP and MUC5B modulate the effect of ambient NO2 on respiratory symptoms in infancy. Chemosphere, 363, p. 142837. Elsevier Science 10.1016/j.chemosphere.2024.142837

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BACKGROUND

Current knowledge suggests that the gene region containing MUC5B and TOLLIP plays a role in airway defence and airway inflammation, and hence respiratory disease. It is also known that exposure to air pollution increases susceptibility to respiratory disease. We aimed to study whether the effect of air pollutants on the immune response and respiratory symptoms in infants may be modified by polymorphisms in MUC5B and TOLLIP genes.

METHODS

359 healthy term infants from the prospective Basel-Bern Infant Lung Development (BILD) birth cohort were included in the study. The main outcome was the score of weekly assessed respiratory symptoms in the first year of life. Using the candidate gene approach, we selected 10 single nucleotide polymorphisms (SNPs) from the MUC5B and TOLLIP regions. Nitrogen dioxide (NO2) and particulate matter ≤10μm in aerodynamic diameter (PM10) exposure was estimated on a weekly basis. We used generalised additive mixed models adjusted for known covariates. To validate our results in vitro, cells from a lung epithelial cell line were downregulated in TOLLIP expression and exposed to diesel particulate matter (DPM) and polyinosinic-polycytidylic acid.

RESULTS

Significant interaction was observed between modelled air pollution (weekly NO2 exposure) and 5 SNPs within MUC5B and TOLLIP genes regarding respiratory symptoms as outcome: E.g., infants carrying minor alleles of rs5744034, rs3793965 and rs3750920 (all TOLLIP) had an increased risk of respiratory symptoms with increasing NO2 exposure. In vitro experiments showed that cells downregulated for TOLLIP react differently to environmental pollutant exposure with DPM and viral stimulation.

CONCLUSION

Our findings suggest that the effect of air pollution on respiratory symptoms in infancy may be influenced by the genotype of specific SNPs from the MUC5B and TOLLIP regions. For validation of the findings, we provided in vitro evidence for the interaction of TOLLIP with air pollution.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pneumologie (Pädiatrie)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Pneumology

UniBE Contributor:

Soti, Andras Laszlo, Steinberg, Ruth Theresia, Bovermann, Xenia Ursula, Latzin, Philipp, Müller, Loretta Lina (A)

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0045-6535

Publisher:

Elsevier Science

Language:

English

Submitter:

Pubmed Import

Date Deposited:

17 Jul 2024 15:18

Last Modified:

21 Aug 2024 00:14

Publisher DOI:

10.1016/j.chemosphere.2024.142837

PubMed ID:

39009092

Uncontrolled Keywords:

MUC5B TOLLIP air pollution gene–environment interaction infancy respiratory symptoms

BORIS DOI:

10.48350/199031

URI:

https://boris.unibe.ch/id/eprint/199031

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