Increased Homocysteine and S-Adenosylhomocysteine Concentrations and DNA Hypomethylation in Vascular Disease

Castro, Rita; Rivera, Isabel; Struys, Eduard A.; Jansen, Erwin E.W.; Ravasco, Paula; Camilo, M.; Blom, Henk J.; Jakobs, Cornelis; Almeida, Isabel Tavares de

doi:10.1373/49.8.1292

Cited by 369 publications

(249 citation statements)

References 18 publications

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“…Several population studies have demonstrated a strong correlation between folate status and coronary artery disease. Patients with the atherosclerotic vascular disease often exhibit higher homocysteine and Sadenosylhomocysteine (SAHC) and lower genomic DNA methylation status [50]. However, no specific genes have been identified as the target of reduced methylation in these patients.…”

Section: Dietary Factorsmentioning

confidence: 99%

Epigenetic reprogramming and imprinting in origins of disease

Tang

2007

Rev Endocr Metab Disord

212

134

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The traditional view that gene and environment interactions control disease susceptibility can now be expanded to include epigenetic reprogramming as a key determinant of origins of human disease. Currently, epigenetics is defined as heritable changes in gene expression that do not alter DNA sequence but are mitotically and trans-generationally inheritable. Epigenetic reprogramming is the process by which an organism's genotype interacts with the environment to produce its phenotype and provides a framework for explaining individual variations and the uniqueness of cells, tissues, or organs despite identical genetic information. The main epigenetic mediators are histone modification, DNA methylation, and non-coding RNAs. They regulate crucial cellular functions such as genome stability, X-chromosome inactivation, gene imprinting, and reprogramming of non-imprinting genes, and work on developmental plasticity such that exposures to endogenous or exogenous factors during critical periods permanently alter the structure or function of specific organ systems. Developmental epigenetics is believed to establish "adaptive" phenotypes to meet the demands of the later-life environment. Resulting phenotypes that match predicted later-life demands will promote health, while a high degree of mismatch will impede adaptability to later-life challenges and elevate disease risk. The rapid introduction of synthetic chemicals, medical interventions, environmental pollutants, and lifestyle choices, may result in conflict with the programmed adaptive changes made during early development, and explain the alarming increases in some diseases. The recent identification of a significant number of epigenetically regulated genes in various model systems has prepared the field to take on the challenge of characterizing distinct epigenomes related to various diseases. Improvements in human health could then be redirected from curative care to personalized, preventive medicine based, in part, on epigenetic markings etched in the "margins" of one's genetic make-up. NIH Public Access Author ManuscriptRev Endocr Metab Disord. Author manuscript; available in PMC 2014 June 13. Epigenetics meets genetics in disease susceptibilityIn the past, susceptibility of disease was believed to be determined solely by inheritable information carried on the primary sequence of the DNA. Individuals are endowed with different genotypes that dictate how they respond to endogenous factors such as development cues, hormones, and cytokines or to exogenous influences, including nutrient availability, infection, physical activities, social behavior, and other environmental factors. Over time, these responses form the basis of genetic variability to disease susceptibility. Aberrant changes in linear DNA sequence result in mutations, deletions, gene fusion, tandem duplications, or gene amplifications causing dysregulation of gene expression that underlies the genesis of disease [1][2][3][4][5][6][7]. Recently, however, it has become clear that epigenetic disr...

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Section: Dietary Factorsmentioning

confidence: 99%

Epigenetic reprogramming and imprinting in origins of disease

Tang

2007

Rev Endocr Metab Disord

212

134

View full text Add to dashboard Cite

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“…The literature to date indicates that DNA methylation may be an important pathway linking particulate matter (PM) to health outcomes. [6][7][8][9][10] For example, changes in patterns of DNA methylation may be associated with processes leading to cardiovascular diseases.. 11,12 There is growing evidence that exposure to PM is associated with global DNA methylation and gene-specific methylation, 6,7,13,14 especially for exposure to metal-rich PM in occupational settings. 15, 16 Yet, little is known regarding how PM exposure affects DNA methylation on a genome-wide level.…”

Section: Introductionmentioning

confidence: 99%

Differential DNA methylation and PM_2.5 species in a 450K epigenome-wide association study

et al. 2017

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Although there is growing evidence that exposure to ambient particulate matter is associated with global DNA methylation and gene-specific methylation, little is known regarding epigenome-wide changes in DNA methylation in relation to particles and, especially, particle components. Using the Illumina Infinium HumanMethylation450 BeadChip, we examined the relationship between one-year moving averages of PM 2.5 species (Al, Ca, Cu, Fe, K, Na, Ni, S, Si, V, and Zn) and DNA methylation at 484,613 CpG probes in a longitudinal cohort that included 646 subjects. Bonferroni correction was applied to adjust for multiple comparisons. Bioinformatics analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was also performed. We observed 20 Bonferroni significant (P-value < 9.4£ 10 ¡9 ) CpGs for Fe, 8 for Ni, and 1 for V. Particularly, methylation at Schlafen Family Member 11 (SLFN11) cg10911913 was positively associated with measured levels of all 3 species. The SLFN11 gene codes for an interferoninduced protein that inhibits retroviruses and sensitizes cancer cells to DNA-damaging agents. Bioinformatics analysis suggests that gene targets may be relevant to pathways including cancers, signal transduction, and cell growth and death. Ours is the first study to examine the epigenome-wide association between ambient particles species and DNA methylation. We found that long-term exposures to specific components of ambient particle pollution, especially particles emitted during oil combustion, were associated with methylation changes in genes relevant to immune responses. Our findings provide insight into potential biologic mechanisms on an epigenetic level.

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“…In patients with vascular disease, Castro et al (2003) reported significantly higher plasma homocysteine and SAH concentrations in association with leukocyte DNA hypomethylation, without concomitant changes in plasma SAM concentration. In an animal model, a decrease in the SAM/SAH ratio was predictive of reduced methylation capacity only when associated with an increase in SAH; a decrease in the SAM/SAH ratio due to SAM depletion alone was not sufficient to affect DNA methylation (Caudill et al, 2001).…”

Section: Resultsmentioning

confidence: 89%

Folate status and S-adenosylmethionine/S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans

et al. 2007

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Objectives: This study reports the influence of colorectal neoplasia on methylation intermediates and folate concentrations in human colonic mucosa, as well as systemic measures of folate status, to examine biomarkers and possible mechanisms of folaterelated carcinogenesis. Subjects: A total of 47 patients were selected from those previously diagnosed with adenocarcinoma of the colorectum undergoing surgery. For each individual, we obtained a biopsy of the adenocarcinoma and a biopsy of normal appearing mucosa, to perform an intra-individual comparison. Results: The 'methylation' ratio (S-adenosylmethionine/S-adenosylhomocysteine (SAH)) was lower in pathological tissue vs normal mucosa (P ¼ 0.08), mainly due to a much higher SAH concentration (Po0.005). Colonic folate concentration was significantly diminished in malignant tissue (Po0.0001). Plasma homocysteine concentration was within the normal to high range, and folate and vitamin B12 plasma concentrations were within the low to normal range as compared with normative values. Conclusion: Our results contribute to the hypothesis that altered DNA methylation and methyl metabolism is associated with colorectal neoplasia.

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Increased Homocysteine and S-Adenosylhomocysteine Concentrations and DNA Hypomethylation in Vascular Disease

Cited by 369 publications

References 18 publications

Epigenetic reprogramming and imprinting in origins of disease

Epigenetic reprogramming and imprinting in origins of disease

Differential DNA methylation and PM_2.5 species in a 450K epigenome-wide association study

Folate status and S-adenosylmethionine/S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans

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Increased Homocysteine and S-Adenosylhomocysteine Concentrations and DNA Hypomethylation in Vascular Disease

Cited by 369 publications

References 18 publications

Epigenetic reprogramming and imprinting in origins of disease

Epigenetic reprogramming and imprinting in origins of disease

Differential DNA methylation and PM2.5 species in a 450K epigenome-wide association study

Folate status and S-adenosylmethionine/S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans

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Differential DNA methylation and PM_2.5 species in a 450K epigenome-wide association study