Novel Epigenetic Changes Unveiled by Monozygotic Twins Discordant for Smoking Habits

Allione, Alessandra; Marcon, Francesca; Fiorito, Giovanni; Guarrera, Simonetta; Siniscalchi, Ester; Zijno, Andrea; Crebelli, Riccardo; Matullo, Giuseppe

doi:10.1371/journal.pone.0128265

Cited by 50 publications

(50 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the average differences between cases and healthy controls were lower than 10%. Further, hypo‐methylation at F2RL3 gene was strongly associated with smoking habits (Zhang et al, ; Allione et al, ; Fasanelli et al, ), a known risk factor for CCVD, suggesting F2RL3 gene as a potential mediator in the association of smoking with CCVD (Breitling et al, ). The evidence above suggested us to consider the results of the single CpG analyses carefully.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress and inflammation mediate the effect of air pollution on cardio‐ and cerebrovascular disease: A prospective study in nonsmokers

Fiorito

Vlaanderen

Polidoro

et al. 2017

Environ and Mol Mutagen

Self Cite

View full text Add to dashboard Cite

Air pollution is associated with a broad range of adverse health effects, including mortality and morbidity due to cardio- and cerebrovascular diseases (CCVD), but the molecular mechanisms involved are not entirely understood. This study aims to investigate the involvement of oxidative stress and inflammation in the causal chain, and to identify intermediate biomarkers that are associated retrospectively with the exposure and prospectively with the disease. We designed a case-control study on CCVD nested in a cohort of 18,982 individuals from the EPIC-Italy study. We measured air pollution, inflammatory biomarkers, and whole-genome DNA methylation in blood collected up to 17 years before the diagnosis. The study sample includes all the incident CCVD cases among former- and never-smokers, with available stored blood sample, that arose in the cohort during the follow-up. We identified enrichment of altered DNA methylation in "ROS/Glutathione/Cytotoxic granules" and "Cytokine signaling" pathways related genes, associated with both air pollution (multiple comparisons adjusted p for enrichment ranging from 0.01 to 0.03 depending on pollutant) and with CCVD risk (P = 0.04 and P = 0.03, respectively). Also, Interleukin-17 was associated with higher exposure to NO (P = 0.0004), NO (P = 0.0005), and CCVD risk (OR = 1.79; CI 1.04-3.11; P = 0.04 comparing extreme tertiles). Our findings indicate that chronic exposure to air pollution can lead to oxidative stress, which in turn activates a cascade of inflammatory responses mainly involving the "Cytokine signaling" pathway, leading to increased risk of CCVD. Inflammatory proteins and DNA methylation alterations can be detected several years before CCVD diagnosis in blood samples, being promising preclinical biomarkers. Environ. Mol. Mutagen. 59:234-246, 2018. © 2017 Wiley Periodicals, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

Oxidative stress and inflammation mediate the effect of air pollution on cardio‐ and cerebrovascular disease: A prospective study in nonsmokers

Fiorito

Vlaanderen

Polidoro

et al. 2017

Environ and Mol Mutagen

Self Cite

View full text Add to dashboard Cite

show abstract

“…Methylation changes can be caused by external conditions, such as long-term stress exposure (Klengel et al, 2014;Romens et al, 2015), (prenatal, maternal) smoking exposure (Allione et al, 2015;Lee et al, 2015) and dietary modifications at conception (Dominguez-salas et al, 2014). There are no epigenetic studies of the association between DNA methylation and WB, but some epigenetic studies have been performed involving complex traits related to WB.…”

mentioning

confidence: 99%

Epigenome-Wide Association Study of Wellbeing

Baselmans

Dongen

Nivard³

et al. 2015

Twin Res Hum Genet

View full text Add to dashboard Cite

Wellbeing (WB) is a major topic of research across several scientific disciplines, partly driven by its strong association with psychological and mental health. Twin-family studies have found that both genotype and environment play an important role in explaining the variance in WB. Epigenetic mechanisms, such as DNA methylation, regulate gene expression, and may mediate genetic and environmental effects on WB. Here, for the first time, we apply an epigenome-wide association study (EWAS) approach to identify differentially methylated sites associated with individual differences in WB. Subjects were part of the longitudinal survey studies of the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2002 and 2011. WB was assessed by a short inventory that measures satisfaction with life (SAT). DNA methylation was measured in whole blood by the Illumina Infinium HumanMethylation450 BeadChip (HM450k array) and the association between WB and DNA methylation level was tested at 411,169 autosomal sites. Two sites (cg10845147, p = 1.51 * 10−8 and cg01940273, p = 2.34 * 10−8) reached genome-wide significance following Bonferonni correction. Four more sites (cg03329539, p = 2.76* 10−7; cg09716613, p = 3.23 * 10−7; cg04387347, p = 3.95 * 10−7; and cg02290168, p = 5.23 * 10−7) were considered to be genome-wide significant when applying the widely used criterion of a FDR q value < 0.05. Gene ontology (GO) analysis highlighted enrichment of several central nervous system categories among higher-ranking methylation sites. Overall, these results provide a first insight into the epigenetic mechanisms associated with WB and lay the foundations for future work aiming to unravel the biological mechanisms underlying a complex trait like WB.

show abstract

“…In adult smokers, an association with DNA methylation in the AHRR gene was also observed in lymphoblasts and alveolar macrophages. 59 A recent monozygotic twin study 60 found differential methylation between the smoking and nonsmoking twins in eight loci that had been reported in prior studies, including loci in AHRR and F2RL3 . Differential DNA methylation has also been observed with respect to current vs. former smoking, cumulative smoking exposure (e.g., lifetime pack-years of smoking), and time since quitting (among former smokers).…”

Section: Lifestyle Environment Aging and Dna Methylationmentioning

confidence: 77%

The Role of DNA Methylation in Cardiovascular Risk and Disease

Zhong

Agha

Baccarelli

2016

Circulation Research

178

View full text Add to dashboard Cite

Epidemiological studies have demonstrated that genetic, environmental, behavioral, and clinical factors contribute to cardiovascular disease (CVD) development. How these risk factors interact at the cellular level to cause CVD is not well known. Epigenetic epidemiology enables researchers to explore critical links between genomic coding, modifiable exposures, and manifestation of disease phenotype. One epigenetic link, DNA methylation, is potentially an important mechanism underlying these associations. In the past decade, there has been a significant increase in the number of epidemiological studies investigating cardiovascular risk factors and outcomes in relation to DNA methylation, but many gaps remain in our understanding of the underlying etiology and biological implications. In this review we provide a brief overview of the biology and mechanisms of DNA methylation and its role in CVD. In addition, we summarize the current evidence base in epigenetic epidemiology studies relevant to cardiovascular health and disease, and discuss the limitations, challenges, and future directions of the field. Finally, we provide guidelines for well-designed epigenetic epidemiology studies, with particular focus on methodological aspects, study design, and analytical challenges.

show abstract

Novel Epigenetic Changes Unveiled by Monozygotic Twins Discordant for Smoking Habits

Cited by 50 publications

References 37 publications

Oxidative stress and inflammation mediate the effect of air pollution on cardio‐ and cerebrovascular disease: A prospective study in nonsmokers

Oxidative stress and inflammation mediate the effect of air pollution on cardio‐ and cerebrovascular disease: A prospective study in nonsmokers

Epigenome-Wide Association Study of Wellbeing

The Role of DNA Methylation in Cardiovascular Risk and Disease

Contact Info

Product

Resources

About