Genetic susceptibility in air pollution-induced airway inflammation in elderly women

Abstract

BACKGROUND AND AIM: Evidence is supporting that air pollutants can activate inflammatory responses which increase oxidative stress and further affect respiratory health. So far, epidemiological studies on this pathway have mainly disregarded genetic effects. Thus, we aim to investigate the role of genetic susceptibility in air pollution-induced airway inflammation. METHODS: We used data from 445 women (68–79 years) enrolled in the ongoing cohort study on the influence of air pollution on lung function, inflammation and aging (SALIA) between baseline (years 1984–94) and first follow-up (years 2007–10). Biomarkers of airway inflammation were determined at follow-up in induced-sputum samples (levels of leukotriene (LT)B4, tumour necrosis factor-α (TNF-α), the total number of cells and nitric oxide derivatives). Out of 272 lung function-related single nucleotide polymorphisms, we calculated biomarker-specific weighted genetic risk scores (GRS) using internal weights from elastic net regression. Interactions between GRS and chronic NO2, NOx, PM2.5, PM10, PMcoarse, and PM2.5 absorbance exposure (the centred means of cumulative exposure to each air pollutant over observation time) on inflammation were investigated by adjusted linear regression models. RESULTS:Our results confirm that higher exposure to each air pollutant increase airway inflammation (TNF-α) and additionally, higher exposure to PMcoarse increases LTB4 level. Furthermore, we observed significant gene-environment interaction effects for TNF-α (adj. GRSxNOx: p-value=0.036, adj. GRSxPM2.5: p-value=0.021, adj. GRSxPMcoarse: p-value=0.001) and for LTB4 (adj. GRSxPMcoarse: p-value=0.001). Women with high GRS compared to low GRS had an increased risk of air pollution-induced higher TNF-α level as well as higher LTB4 level. CONCLUSIONS:Genetic susceptibility may play a role in the pathway of chronic air pollution exposure to airway inflammation responses. KEYWORDS: Air pollution, Epigenomics, Female, Long-term exposure, Respiratory outcomes, Risk assessment