Smoking alters the DNA Methylation of the Olfactory Sensing System

Smoking as a major risk factor for the general ill-health and chronic diseases affect numerous regulatory systems of the human body, which respond to the damage by altering the gene expression through the epigenetic regulatory machinery. Previous studies have discovered that numerous DNA methylation sites are affected by the tobacco exposure and many cardiovascular disease, cancer, and immune system related pathways altered, potentially mediating the pathophysiological responses. This study identifies three novel methylation sites and the olfactory sensing pathways as altered in the current smokers in comparison with the never-smokers. The epigenome-wide association study replicated 57 altered cytocine-guanine (CpG) methylation sites and identified 3 novel sites having potential role in smoking associated disease (cg26038589 in gene CCDC55, cg10385208 in gene CCDC49, cg09355027 without gene). In the Molecular Signature Database (MSigDB) based pathway analysis, the most enriched gene ontology biological process was the sensory perception of chemical stimulus followed closely by the related signaling pathways, while the highest ranking canonical pathways were the Reactome olfactory signaling and the KEGG olfactory transduction. The other significant pathways replicated the previous results regarding cardiovascular disease, cancer, and immune system. It is concluded that the highly regenerating olfactory system responds to the tobacco smoke and toxin exposure through mechanisms, which involve the epigenetic regulatory machinery, identified based on the differentially methylated genes and pathways. The originality of this thesis has been verified using the Turnitin OriginalityCheck software, as specified by the Quality System of the University of Tampere