title: Waterpipe smoking induces epigenetic changes in the small airway epithelium.
abstract: Waterpipe (also called hookah, shisha, or narghile) smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use waterpipe smoking on DNA methylation of the small airway epithelium (SAE) and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk) waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05) representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05) change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling). Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Walters
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Salit
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Ju
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Staudt
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.|Department of Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kaner
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Rogalski
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Teniola B
authors.initials: TB
authors.lastname: Sodeinde
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Riyaad
authors.initials: R
authors.lastname: Rahim
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Yael
authors.initials: Y
authors.lastname: Strulovici-Barel
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Mezey
authors.affiliation: Pulmonary Section, Hamad Medical Corporation, Doha, Qatar.
authors.forename: Ahmad M
authors.initials: AM
authors.lastname: Almulla
authors.affiliation: Pulmonary Section, Hamad Medical Corporation, Doha, Qatar.
authors.forename: Hisham
authors.initials: H
authors.lastname: Sattar
authors.affiliation: Weill Cornell Medical College-Qatar, Doha, Qatar.
authors.forename: Mai
authors.initials: M
authors.lastname: Mahmoud
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.|Department of Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000328:Adult; D001980:Bronchi / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D012313:RNA / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012907:Smoking; D015854:Up-Regulation
chemical_list: D018336:Receptors, Aryl Hydrocarbon; D043562:Receptors, G-Protein-Coupled; D012313:RNA; D004247:DNA