The role of epigenetic modifications in cardiovascular disease: A systematic review

Muka, Taulant; Koromani, Fjorda; Portilla, Eliana; O’Connor, Annalouise; Bramer, Wichor M.; Troup, J. P.; Chowdhury, Rajiv; Dehghan, Abbas; Franco, Oscar H.

doi:10.1016/j.ijcard.2016.03.062

Cited by 148 publications

(98 citation statements)

References 82 publications

(119 reference statements)

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“…These results are in line with those of studies that showed a link between LINE-1 hypomethylation and CVD, especially hypertension [16, 50, 51]. It should be noted here that sex differences are also known to be present in other diseases caused by chronic exposure to arsenic.…”

Section: Discussionsupporting

confidence: 93%

“…Methylation at LINE-1 repeats is gaining increasing attention as a surrogate marker to distinguish normal from pathological disease tissue [57]. Decreased methylation of LINE-1 sequences in blood leukocyte DNA has been documented in many human cancers and other chronic diseases [12–16] Therefore, LINE-1 hypomethylation in blood leukocyte-derived DNA caused by chronic exposure to arsenic may be one of the potential epigenetic mechanisms of arsenic-induced chronic diseases, including hypertension.…”

Section: Discussionmentioning

confidence: 99%

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Chronic exposure to arsenic, LINE-1 hypomethylation, and blood pressure: a cross-sectional study in Bangladesh

et al. 2017

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BackgroundChronic exposure to arsenic is associated with cancer and hypertension. Growing evidence suggests that altered methylation in long interspersed nuclear element-1 (LINE-1) is involved in many types of disorders, including cardiovascular disease. Here we evaluated the association between arsenic exposure and LINE-1 methylation levels, especially in relation to blood pressure (BP).MethodsA total of 236 subjects (175 from arsenic-endemic areas and 61 from a non-endemic area) in rural Bangladesh were recruited. The subjects’ arsenic exposure levels (i.e., drinking water, hair and nail arsenic concentrations) were measured by inductively coupled plasma mass spectroscopy. The subjects’ LINE-1 methylation levels were determined by pyrosequencing.ResultsThe average LINE-1 methylation levels of the subjects living in the arsenic-endemic areas were significantly (p < 0.01) lower than those of the subjects living in the non-endemic area. In a sex-stratified analysis, the arsenic exposure levels in female but not male subjects showed a significant inverse association with LINE-1 methylation levels before (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) and after (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) adjustment for age, body mass index and smoking. Analyses examining interactions among arsenic levels, BP and LINE-1 methylation showed that arsenic-related elevated levels of BP were associated with LINE-1 hypomethylation.ConclusionsOur findings demonstrated that chronic exposure to arsenic was inversely associated with LINE-1 methylation levels in blood leukocyte DNA and this was more pronounced in females than males; in addition, the decreased levels of LINE-1 methylation might be involved in the arsenic-induced elevation of BP.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-017-0231-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Chronic exposure to arsenic, LINE-1 hypomethylation, and blood pressure: a cross-sectional study in Bangladesh

et al. 2017

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“…These results are in line with previous studies showing contradictory results when studying the relationship between global DNA methylation and other health outcomes, including cardiovascular disease and diabetes [85–91]. The use of different methods for assessing global DNA methylation, including the 5-methylcytosine ratio and the methylation of LINE-1 and Alu repeat elements, may account for some of these differences.…”

Section: Discussionsupporting

confidence: 90%

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

et al. 2016

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ImportanceEpigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD).ObjectiveTo systematically review studies investigating epigenetic marks in AD or PD.MethodsEleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form.ResultsOf 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD.ConclusionMany studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.

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“…DNA methylation (global and gene-specific) is a plausible biological mediator of CVD/RD-related events (44)(45)(46)(47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

Possible Mediation by Methylation in Acute Inflammation Following Personal Exposure to Fine Particulate Air Pollution

Wang

Chen

Shi

et al. 2017

American Journal of Epidemiology

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Air pollution may increase cardiovascular and respiratory risk through inflammatory pathways, but evidence for acute effects has been weak and indirect. Between December 2014 and July 2015, we enrolled 36 healthy, nonsmoking college students for a panel study in Shanghai, China, a city with highly variable levels of air pollution. We measured personal exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM 2.5 ) continuously for 72 hours preceding each of 4 clinical visits that included phlebotomy. We measured 4 inflammation proteins and DNA methylation at nearby regulatory cytosine-phosphate-guanine (CpG) loci. We applied linear mixed-effect models to examine associations over various lag times. When results suggested mediation, we evaluated methylation as mediator. Increased PM 2.5 concentration was positively associated with all 4 inflammation proteins and negatively associated with DNA methylation at regulatory loci for tumor necrosis factor alpha (TNF-α) and soluble intercellular adhesion molecule-1. A 10-μg/m 3 increase in average PM 2.5 during the 24 hours preceding blood draw corresponded to a 4.4% increase in TNF-α and a statistically significant decrease in methylation at one of the two studied candidate CpG loci for TNF-α. Epigenetics may play an important role in mediating effects of PM 2.5 on inflammatory pathways. DNA methylation; fine particulate matter; inflammation; mediation analysis; panel study; personal exposure Abbreviations: CI, confidence interval; CpG, cytosine-phosphate-guanine; CVD, cardiovascular disease; PM, particulate matter; PM 2.5 , particulate matter having an aerodynamic diameter less than or equal to 2.5 μm; RD, respiratory disease; sCD40L, soluble cluster of differentiation 40 (CD40) ligand; sICAM-1, soluble intercellular adhesion molecule-1; TNF-α, tumor necrosis factor alpha.

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The role of epigenetic modifications in cardiovascular disease: A systematic review

Cited by 148 publications

References 82 publications

Chronic exposure to arsenic, LINE-1 hypomethylation, and blood pressure: a cross-sectional study in Bangladesh

Chronic exposure to arsenic, LINE-1 hypomethylation, and blood pressure: a cross-sectional study in Bangladesh

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

Possible Mediation by Methylation in Acute Inflammation Following Personal Exposure to Fine Particulate Air Pollution

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