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• W4303616271 endingPage "104301" @default.
• W4303616271 startingPage "104301" @default.
• W4303616271 abstract "Mitochondrial DNA copy number (mtCN) maintains cellular function and homeostasis, and is linked to nuclear DNA methylation and gene expression. Increased mtCN in the blood is associated with smoking and respiratory disease, but has received little attention for target organ effects for smoking or electronic cigarette (EC) use.Bronchoscopy biospecimens from healthy EC users, smokers (SM), and never-smokers (NS) were assessed for associations of mtCN with mtDNA point mutations, immune responses, nuclear DNA methylation and gene expression using linear regression. Ingenuity pathway analysis was used for enriched pathways. GEO and TCGA respiratory disease datasets were used to explore the involvement of mtCN-associated signatures.mtCN was higher in SM than NS, but EC was not statistically different from either. Overall there was a negative association of mtCN with a point mutation in the D-loop but no difference within groups. Positive associations of mtCN with IL-2 and IL-4 were found in EC only. mtCN was significantly associated with 71,487 CpGs and 321 transcripts. 263 CpGs were correlated with nearby transcripts for genes enriched in the immune system. EC-specific mtCN-associated-CpGs and genes were differentially expressed in respiratory diseases compared to controls, including genes involved in cellular movement, inflammation, metabolism, and airway hyperresponsiveness.Smoking may elicit a lung toxic effect through mtCN. While the impact of EC is less clear, EC-specific associations of mtCN with nuclear biomarkers suggest exposure may not be harmless. Further research is needed to understand the role of smoking and EC-related mtCN on lung disease risks.The National Cancer Institute, the National Heart, Lung, and Blood Institute, the Food and Drug Administration Center for Tobacco Products, the National Center For Advancing Translational Sciences, and Pelotonia Intramural Research Funds." @default.
• W4303616271 created "2022-10-08" @default.
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• W4303616271 date "2022-11-01" @default.
• W4303616271 modified "2023-10-16" @default.
• W4303616271 title "Lung mitochondrial DNA copy number, inflammatory biomarkers, gene transcription and gene methylation in vapers and smokers" @default.
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• W4303616271 doi "https://doi.org/10.1016/j.ebiom.2022.104301" @default.
• W4303616271 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36215783" @default.
• W4303616271 hasPublicationYear "2022" @default.
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