The relation between DNA methylation patterns and serum cytokine levels in community-dwelling adults: a preliminary study

McEwen, Lisa M.; Kohli, Vikas; Wolfson, Christina; Bowdish, Dawn M. E.; Raina, Parminder; Kobor, Michæl S.; Balion, Cynthia

doi:10.1186/s12863-017-0525-3

Cited by 21 publications

(14 citation statements)

References 51 publications

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“…We found several statistically significant associations, being all but two out of 13 protein biomarkers associated with at least one DNAmIP (Supporting Information Table SIII). Our results reinforce previous knowledge about DNAm regulation of inflammatory biomarkers (Sabunciyan et al, 2015;Ligthart et al, 2016;van Otterdijk et al, 2017), including cytokines (Verschoor et al, 2017) and interleukins (Takahashi et al, 2015), and support the usefulness of omic profiling in peripheral blood, for the early identification of diseaserelated perturbations caused by toxic exposures (Georgiadis et al, 2016).…”

Section: Association Between Protein and Dnam Biomarkerssupporting

confidence: 91%

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

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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.

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Section: Association Between Protein and Dnam Biomarkerssupporting

confidence: 91%

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

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“…One study assessed 121 biomarkers related with inflammation, cancer, and cardiovascular disease [30] and five studies assessed CRP. The remaining two studies evaluated TNF and interleukins such as IL-1 β , IL-6, IL-8, and IL-10 [31, 32] (Table 3).…”

Section: Resultsmentioning

confidence: 99%

Epigenetics and Inflammatory Markers: A Systematic Review of the Current Evidence

González-Jaramillo

Portilla‐Fernandez

Glišić

et al. 2019

International Journal of Inflammation

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Epigenetic mechanisms have been suggested to play a role in the genetic regulation of pathways related to inflammation. Therefore, we aimed to systematically review studies investigating the association between DNA methylation and histone modifications with circulatory inflammation markers in blood. Five bibliographic databases were screened until 21 November of 2017. We included studies conducted on humans that examined the association between epigenetic marks (DNA methylation and/or histone modifications) and a comprehensive list of inflammatory markers. Of the 3,759 identified references, 24 articles were included, involving, 17,399 individuals. There was suggestive evidence for global hypomethylation but better-quality studies in the future have to confirm this. Epigenome-wide association studies (EWAS) (n=7) reported most of the identified differentially methylated genes to be hypomethylated in inflammatory processes. Candidate genes studies reported 18 differentially methylated genes related to several circulatory inflammation markers. There was no overlap in the methylated sites investigated in candidate gene studies and EWAS, except for TMEM49, which was found to be hypomethylated with higher inflammatory markers in both types of studies. The relation between histone modifications and inflammatory markers was assessed by one study only. This review supports an association between epigenetic marks and inflammation, suggesting hypomethylation of the genome. Important gaps in the quality of studies were reported such as inadequate sample size, lack of adjustment for relevant confounders, and failure to replicate the findings. While most of the studies have been focused on C-reactive protein, further efforts should investigate other inflammatory markers.

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“…This led to the identification of 18 novel loci that were not identified using genotyped or imputed SNPs [36]. A number of studies have also carried out epigenome-wide association studies (EWAS) on the levels of a small set of inflammatory proteins, including C-reactive protein, interleukins-(1β, 4, 6, 9 and 10), interferon-gamma, transforming growth factor-beta and tumour necrosis factor [37][38][39][40][41][42]. Zaghlool et al performed an EWAS of 1123 proteins, which pointed towards networks of chronic low-grade inflammatory biomarkers (n = 944 individuals) [43].…”

Section: Introductionmentioning

confidence: 99%

Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults

et al. 2020

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Background: The molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear modelbased methods which may fail to account for complex structure and interrelationships within molecular datasets. Methods: In this study, we perform genome-and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares-(OLS) and mixed model-based approaches). Results: We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified 3 CpG sites spread across 3 proteins (n = 1 CpG each) that were concordant across OLS, mixedmodel and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to 1 polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease and between IL12B and Crohn's disease. Conclusions: Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.

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The relation between DNA methylation patterns and serum cytokine levels in community-dwelling adults: a preliminary study

Cited by 21 publications

References 51 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

Epigenetics and Inflammatory Markers: A Systematic Review of the Current Evidence

Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults

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