GSE169757
Vaping but not past smoking is significantly associated with dysregulation of genes in blood leukocytes: targeting of mitochondrial and immune response genes
Background: Adult vapers are likely to co-use electronic cigarettes (e-cigs) and combustible cigarettes or have a prior history of smoking. Teasing out the health consequences of vaping in adults, while accounting for the confounding effects of smoking, remains a research priority. Methods: We have segregated the biological effects of vaping from smoking by constructing the whole transcriptome in leukocytes of healthy adult vapers (with and without a history of smoking) and exclusive smokers in comparison to control nonsmokers non-vapers (n = 37, 22, 23, respectively). Results: Age- and sex-adjusted limmaVoom analysis of RNA-seq data showed significant dysregulation of key genes and molecular pathways in both vapers and smokers as compared to controls. The extent of transcriptomic effects, as reflected by the number of differentially expressed genes, was more pronounced in smokers than vapers (683 vs. 92). Computational modeling, combining primary and sensitivity analyses, revealed that e-cig use, but not past smoking, is significantly associated with gene dysregulation in vapers. Comparative analysis of the gene networks and canonical pathways impacted in vapers and smokers showed strikingly similar biological outcomes in the two groups, although the number of affected genes was several-fold higher in smokers than vapers. Of significance is the preferential targeting of mitochondrial genes in both vapers and smokers, consistent with impaired functional networks, which are known to drive mitochondrial DNA-related disorders. Equally remarkable is the dysregulation of immune response genes in both vapers and smokers, modulated by upstream cytokines, including members of the interleukin and interferon family, that play a crucial role in inflammation. Conclusions: The concurrent targeting of mitochondrial- and immune response genes in vapers and smokers suggests a consequential role for vaping and smoking in inflammation. Our findings accord with the growing evidence on the central role of mitochondria as signaling organelles that govern fundamentals of immunity and inflammatory response. In view of the widespread use of e-cigs among youth and young adults, these novel findings have significant implications for tobacco regulatory science and public health. Overall design: (N=82 total); Experimental 1: Vapers (N=37); Experminemtal 2: Smokers (N=22); Controls | Nonsmokers non-vapers (N=23). No replicate sample is included.