Genetic susceptibility for air pollution-induced airway inflammation in the SALIA study

Long-term air pollution exposure has been associated with chronic inflammation providing a link to the development of chronic health effects. Furthermore, there is evidence that pathways activated by endoplasmatic reticulum (ER) stress induce airway inflammation and thereby play an important role in the pathogenesis of inflammatory diseases.

We investigated the role of genetic variation of the ER stress pathway on air pollution-induced inflammation.

We used the follow-up examination of the German SALIA study (N=402, age 68-79 years). Biomarkers of inflammation were determined in induced sputum. We calculated biomarker-specific weighted genetic risk scores (GRS) out of eight ER stress related single nucleotide polymorphisms and tested their interaction with PM_2.5, PM_2.5 absorbance, PM₁₀ and NO₂ exposure on inflammation by adjusted linear regression.

Genetic variation of the ER stress pathway was associated with higher concentration of inflammation-related biomarkers (levels of leukotriene (LT)B₄, tumor necrosis factor-α (TNF-α), the total number of cells and nitric oxide (NO) derivatives). Furthermore, we observed a significant interaction between air pollution exposure and the ER stress risk score on the concentration of inflammation-related biomarkers. The strongest gene-environment interaction was found for LTB₄ (PM_2.5: p-value=0.002, PM_2.5 absorbance: p-value=0.002, PM₁₀: p-value=0.001 and NO₂: p-value=0.004). Women with a high GRS had a 38% (95%-CI: 16-64%) higher LTB₄ level for an increase of 2.06μg/m³(IQR) in PM_2.5 (no associations in women with a low GRS).

These results indicate that genetic variation in the ER stress pathway might play a role in air pollution induced inflammation in the lung.