Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship

Abstract Cigarette smoking is an established environmental risk factor for Multiple Sclerosis (MS), a chronic inflammatory and neurodegenerative disease, although a mechanistic basis remains largely unknown. We aimed at investigating how smoking affects blood DNA methylation in MS patients, by assay...

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Autores principales:	Francesco Marabita, Malin Almgren, Louise K. Sjöholm, Lara Kular, Yun Liu, Tojo James, Nimrod B. Kiss, Andrew P. Feinberg, Tomas Olsson, Ingrid Kockum, Lars Alfredsson, Tomas J. Ekström, Maja Jagodic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fff67ede152e42ca99d2c835f14f77b1
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spelling	oai:doaj.org-article:fff67ede152e42ca99d2c835f14f77b12021-12-02T11:40:30ZSmoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship10.1038/s41598-017-14788-w2045-2322https://doaj.org/article/fff67ede152e42ca99d2c835f14f77b12017-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-14788-whttps://doaj.org/toc/2045-2322Abstract Cigarette smoking is an established environmental risk factor for Multiple Sclerosis (MS), a chronic inflammatory and neurodegenerative disease, although a mechanistic basis remains largely unknown. We aimed at investigating how smoking affects blood DNA methylation in MS patients, by assaying genome-wide DNA methylation and comparing smokers, former smokers and never smokers in two Swedish cohorts, differing for known MS risk factors. Smoking affects DNA methylation genome-wide significantly, an exposure-response relationship exists and the time since smoking cessation affects methylation levels. The results also show that the changes were larger in the cohort bearing the major genetic risk factors for MS (female sex and HLA risk haplotypes). Furthermore, CpG sites mapping to genes with known genetic or functional role in the disease are differentially methylated by smoking. Modeling of the methylation levels for a CpG site in the AHRR gene indicates that MS modifies the effect of smoking on methylation changes, by significantly interacting with the effect of smoking load. Alongside, we report that the gene expression of AHRR increased in MS patients after smoking. Our results suggest that epigenetic modifications may reveal the link between a modifiable risk factor and the pathogenetic mechanisms.Francesco MarabitaMalin AlmgrenLouise K. SjöholmLara KularYun LiuTojo JamesNimrod B. KissAndrew P. FeinbergTomas OlssonIngrid KockumLars AlfredssonTomas J. EkströmMaja JagodicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francesco Marabita Malin Almgren Louise K. Sjöholm Lara Kular Yun Liu Tojo James Nimrod B. Kiss Andrew P. Feinberg Tomas Olsson Ingrid Kockum Lars Alfredsson Tomas J. Ekström Maja Jagodic Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship
description	Abstract Cigarette smoking is an established environmental risk factor for Multiple Sclerosis (MS), a chronic inflammatory and neurodegenerative disease, although a mechanistic basis remains largely unknown. We aimed at investigating how smoking affects blood DNA methylation in MS patients, by assaying genome-wide DNA methylation and comparing smokers, former smokers and never smokers in two Swedish cohorts, differing for known MS risk factors. Smoking affects DNA methylation genome-wide significantly, an exposure-response relationship exists and the time since smoking cessation affects methylation levels. The results also show that the changes were larger in the cohort bearing the major genetic risk factors for MS (female sex and HLA risk haplotypes). Furthermore, CpG sites mapping to genes with known genetic or functional role in the disease are differentially methylated by smoking. Modeling of the methylation levels for a CpG site in the AHRR gene indicates that MS modifies the effect of smoking on methylation changes, by significantly interacting with the effect of smoking load. Alongside, we report that the gene expression of AHRR increased in MS patients after smoking. Our results suggest that epigenetic modifications may reveal the link between a modifiable risk factor and the pathogenetic mechanisms.
format	article
author	Francesco Marabita Malin Almgren Louise K. Sjöholm Lara Kular Yun Liu Tojo James Nimrod B. Kiss Andrew P. Feinberg Tomas Olsson Ingrid Kockum Lars Alfredsson Tomas J. Ekström Maja Jagodic
author_facet	Francesco Marabita Malin Almgren Louise K. Sjöholm Lara Kular Yun Liu Tojo James Nimrod B. Kiss Andrew P. Feinberg Tomas Olsson Ingrid Kockum Lars Alfredsson Tomas J. Ekström Maja Jagodic
author_sort	Francesco Marabita
title	Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship
title_short	Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship
title_full	Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship
title_fullStr	Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship
title_full_unstemmed	Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship
title_sort	smoking induces dna methylation changes in multiple sclerosis patients with exposure-response relationship
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fff67ede152e42ca99d2c835f14f77b1
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Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship

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