Smoking alters gene expression and methylation patterns in asthma patient nasal epithelium

Current-smoking significantly contributes to worse asthma prognosis and more severe disease symptoms. Smoking limits the beneficial effects of corticosteroids by altering the physiological response in the airways. The nasal epithelium is a relevant site to investigate smoking-related molecular changes as it can reflect the lower airways. As such, we explore the relationship between nasal gene expression and methylation in current and ex-smoker asthma patients. We also investigate how these patterns are altered upon smoking cessation. The analysis was conducted on matched gene expression, and methylation samples collected from nasal brushings of 55 asthma-diagnosed patients. Differential gene expression and methylation analysis compared current vs ex-smokers. Expression quantitative trait methylation analysis was then conducted to explore smoking relevant genes by CpG sites that differ between current and ex-smokers. These sites were compared to a bronchial biopsy smoking-cessation dataset. The analysis was conducted using R software with a false discovery rate (FDR) determined with the Benjamini-Hochberg method. Current smoking in the nose differentially altered 809 genes and 18,814 CpG sites. The cis-eQTM analysis uncovered 171 CpG sites whose methylation status related to the expression of smoking-related genes, including AHRR, ALDH3A1, CYP1A1 and CYP1B1. Methylation of CpG sites altered by current smoking reversed upon one-year of smoking cessation. This study identifies smoking-associated changes in methylation and gene expression are detectable in the nasal epithelium of asthma patients. Our results support the nasal epithelium as an alternate site to investigate changes in the airways due to smoking. We show these patterns are partially reversible after smoking cessation.