title: Genetic susceptibility for air pollution-induced airway inflammation in the SALIA study.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We investigated 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 (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 PM2.5, PM2.5absorbance, PM10and NO2exposure on inflammation by adjusted linear regression.
  
  
  RESULTS
  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(PM2.5: p-value=0.002, PM2.5absorbance: 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 LTB4level for an increase of 2.06μg/m³(IQR) in PM2.5(no associations in women with a low GRS).
  
  
  CONCLUSIONS
  These results indicate that genetic variation in the ER stress pathway might play a role in air pollution induced inflammation in the lung.
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany. Electronic address: Anke.Huels@IUF-Duesseldorf.de.
authors.forename: Anke
authors.initials: A
authors.lastname: Hüls
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Krämer
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Fehsel
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Stolz
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vierkötter
authors.affiliation: IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Schikowski
mesh_terms: D000368:Aged; D000393:Air Pollutants / Q000633:toxicity; D015331:Cohort Studies; D004781:Environmental Exposure; D004784:Environmental Monitoring; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D000393:Air Pollutants
keywords: Endoplasmatic reticulum (ER) stress; Gene-environment interactions; Genetic risk scores; Unfolded protein response (UPR)