Assessment of genetic susceptibilities for air pollution-induced inflammation

Abstract

Introduction: Long-term airborne particle exposure has been associated with chronic inflammation providing a link to long-term health effects of particulate matter (PM). We recently showed an association between PM and increased leukotriene (LT) B4 and tumor necrosis factor-α (TNF-α) measured in induced sputum. Furthermore, there is evidence that pathways activated by the endoplasmatic reticulum (ER) stress response induce sterile inflammation and play an important role in the pathogenesis of obesity, type 2 diabetes, cancer and airway diseases. Therefore, we aimed to estimate the role of genetic variation of the ER stress pathway on air pollution-induced inflammation. Methods: We used the follow-up examination of the German SALIA study of 2008/2009 (N=402, age 68-79 years). Inflammatory biomarkers (LTB4 and TNF-α) were determined in induced sputum. We calculated biomarker-specific weighted genetic risk scores out of eight ER stress related single nucleotide polymorphisms and tested their interaction with PM2.5 and PM10 exposure from land use regression models on inflammation by linear regression analyses adjusting for potential confounders. Results: We observed a significant positive association between the ER stress risk score and both inflammatory biomarkers as well as a significant interaction between PM exposure and the ER stress risk score on LTB4. Women with a high genetic risk score had a 39% (95% CI: 17-66%) higher LTB4 level for an increase of 4.45μg/m³ (IQR) in PM2.5, whereas there were no significant associations in women with a low risk score (only a 3% (95% CI: -11-20%) higher LTB4 level for an increase of 4.45μg/m³ (IQR) in PM2.5). However, these findings were biomarker-specific as the association between PM and TNF-α was not modified by ER stress risk score. Conclusions: These results indicate that genetic variation in the ER stress pathway might play a role in air pollution induced inflammation in the lung.