Transcriptional differences between smokers and non-smokers and variance by obesity as a risk factor for human sensitivity to environmental exposures. (April 2018)

• Record Type: Journal Article
• Authors: Nikodemova, Maria; Yee, Jeremiah; Carney, Patrick R.; Bradfield, Christopher A.; Malecki, Kristen MC.
• Is Part Of: Environment international. Volume 113(2018)
• Page Start: 249
• Page End: 258
• Publication Date: 2018-04
• Subjects: Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2018.02.016
• Languages: English
• ISSNs: 0160-4120

Abstract

Abstract: Background: Obesity has been shown to alter response to air pollution and smoking but underlying biological mechanisms are largely unknown and few studies have explored mechanisms by which obesity increases human sensitivity to environmental exposures. Objective: Overall study goals were to investigate whole blood gene expression in smokers and non-smokers to examine associations between cigarette smoke and changes in gene expression by obesity status and test for effect modification. Methods: Relative fold-change in mRNA expression levels of 84 genes were analyzed using a Toxicity and Stress PCR array among 50 21–54 year old adults. Data on smoking status was confirmed using urinary cotinine levels. Adjusted models included age, gender, white blood cell count and body-mass index. Results: Models comparing gene expression of smokers vs. non-smokers identified six differentially expressed genes associated with smoking after adjustments for covariates. Obesity was associated with 29 genes differentially expressed compared to non-obese. We also identified 9 genes with significant smoking/obesity interactions influencing mRNA levels in adjusted models comparing expression between smokers vs non-smokers for four DNA damage related genes ( GADD45A, DDB2, RAD51 and P53 ), two oxidative stress genes ( FTH1, TXN ), two hypoxia response genes ( BN1P3lL, ARNT ), and one gene associated with unfolded protein response ( ATF6B ). Conclusions: Findings suggest that obesity alters human sensitivity to smoke exposures through sev eral biological pathways by modifying gene expression. Additional studies are needed to fully understand the clinical impact of these effects, but risk assessments should consider underlying phenotypes, such as obesity, that may modulate sensitivity of vulnerable populations to environmental exposures. Highlights: Gene expression is different among obese smokers compared to non-obese smokers. Obesity by smoking interactions influenced the expression of 9 genes in whole blood. Obesity modified DNA damage, oxidative stress and hypoxia pathways in smokers. Findings suggest that obesity modulates sensitivity to toxic effects of smoking.