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Genes, Brain, and Behavior Mar 2020The integration of behavioral epigenetics' principles (eg, DNA methylation) into the study of human infants' development has mainly focused on the effects of early...
The integration of behavioral epigenetics' principles (eg, DNA methylation) into the study of human infants' development has mainly focused on the effects of early adverse exposures, paying less attention to protective caregiving experiences. The present review focused on DNA methylation linked to variations in maternal behavior in human infants and children. Literature search occurred on three databases (PubMed, Scopus and Web of Science) and 11 records were selected. Key variables were abstracted from each article including: sample size and characteristics, time and type of maternal caregiving behavior exposure, time and locus of methylation biomarker, presence/absence, time and type of adverse exposure. Six out of eleven records documented the predictive effect of maternal caregiving on DNA methylation, whereas the remaining five reported on the role of maternal behavior as an influencing factor of the adversity-to-methylation link. Consistent with evidence from the animal model, the quality of maternal caregiving in humans (a) might be associated with variations in DNA methylation status of specific genes involved in socio-emotional development and (b) might partially buffer the association between early adversities and epigenetic variations in infants and children. Current evidence suggests that the quality of maternal caregiving can contribute to behavioral development trajectories of human infants and children at least partially through epigenetic regulation. Open questions and methodological aspects are discussed to guide future human developmental research in behavioral epigenetics.
Topics: Child; Child, Preschool; DNA Methylation; Epigenome; Female; Humans; Infant; Infant, Newborn; Maternal Behavior; Mother-Child Relations; Quantitative Trait Loci
PubMed: 31622002
DOI: 10.1111/gbb.12616 -
Clinical Epigenetics 2015Current evidence supports the notion that environmental exposures are associated with DNA-methylation and expression changes that can impact human health. Our objective... (Review)
Review
Current evidence supports the notion that environmental exposures are associated with DNA-methylation and expression changes that can impact human health. Our objective was to conduct a systematic review of epidemiologic studies evaluating the association between environmental chemicals with DNA methylation levels in adults. After excluding arsenic, recently evaluated in a systematic review, we identified a total of 17 articles (6 on cadmium, 4 on lead, 2 on mercury, 1 on nickel, 1 on antimony, 1 on tungsten, 5 on persistent organic pollutants and perfluorinated compounds, 1 on bisphenol A, and 3 on polycyclic aromatic hydrocarbons). The selected articles reported quantitative methods to determine DNA methylation including immunocolorimetric assays for total content of genomic DNA methylation, and microarray technologies, methylation-specific quantitative PCR, Luminometric Methylation Assay (LUMA), and bisulfite pyrosequencing for DNA methylation content of genomic sites such as gene promoters, LINE-1, Alu elements, and others. Considering consistency, temporality, strength, dose-response relationship, and biological plausibility, we concluded that the current evidence is not sufficient to provide inference because differences across studies and limited samples sizes make it difficult to compare across studies and to evaluate sources of heterogeneity. Important questions for future research include the need for larger and longitudinal studies, the validation of findings, and the systematic evaluation of the dose-response relationships. Future studies should also consider the evaluation of epigenetic marks recently in the research spotlight such as DNA hydroxymethylation and the role of underlying genetic variants.
PubMed: 25984247
DOI: 10.1186/s13148-015-0055-7 -
Journal of Thoracic Oncology : Official... Sep 2021Malignant mesothelioma is an aggressive cancer type linked to asbestos exposure. Because of several intrinsic challenges, mesothelioma is often diagnosed in an advanced... (Meta-Analysis)
Meta-Analysis Review
Malignant mesothelioma is an aggressive cancer type linked to asbestos exposure. Because of several intrinsic challenges, mesothelioma is often diagnosed in an advanced disease stage. Therefore, there is a need for diagnostic biomarkers that may contribute to early detection. Recently, the epigenome of tumors is being extensively investigated to identify biomarkers. This manuscript is a systematic review summarizing the state-of-the-art research investigating DNA methylation in mesothelioma. Four literature databases (PubMed, Scopus, Web of Science, MEDLINE) were systematically searched for studies investigating DNA methylation in mesothelioma up to October 16, 2020. A meta-analysis was performed per gene investigated in at least two independent studies. A total of 53 studies investigated DNA methylation of 97 genes in mesothelioma and are described in a qualitative overview. Furthermore, ten studies investigating 13 genes (APC, CDH1, CDKN2A, DAPK, ESR1, MGMT, miR-34b/c, PGR, RARβ, RASSF1, SFRP1, SFRP4, WIF1) were included in the quantitative meta-analysis. In this meta-analysis, the APC gene is significantly hypomethylated in mesothelioma, whereas CDH1, ESR1, miR-34b/c, PGR, RARβ, SFRP1, and WIF1 are significantly hypermethylated in mesothelioma. The three genes that are the most appropriate candidate biomarkers from this meta-analysis are APC, miR-34b/c, and WIF1. Nevertheless, both study number and study objects comprised in this meta-analysis are too low to draw final conclusions on their clinical applications. The elucidation of the genome-wide DNA methylation profile of mesothelioma is desirable in the future, using a standardized genome-wide methylation analysis approach. The most informative CpG sites from this signature could then form the basis of a panel of highly sensitive and specific biomarkers that can be used for the diagnosis of mesothelioma and even for the screening of an at high-risk population of asbestos-exposed individuals.
Topics: Asbestos; Biomarkers, Tumor; DNA Methylation; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant
PubMed: 34082107
DOI: 10.1016/j.jtho.2021.05.015 -
International Journal of Molecular... Aug 2020Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to... (Review)
Review
Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to better comprehend the evidence on the relationship between epigenetic changes and periodontal disease and its treatment. Therefore, the aim of this systematic review is to identify and synthesize the evidence for an association between DNA methylation/histone modification and periodontal disease and its treatment in human adults. A systematic search was independently conducted to identify articles meeting the inclusion criteria. DNA methylation and histone modifications associated with periodontal diseases, gene expression, epigenetic changes after periodontal therapy, and the association between epigenetics and clinical parameters were evaluated. Sixteen studies were identified. All included studies examined DNA modifications in relation to periodontitis, and none of the studies examined histone modifications. Substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology, was found. There was some evidence, albeit inconsistent, for an association between DNA methylation and periodontal disease. , , , , , and were identified as candidate genes that have been assessed for DNA methylation in periodontitis. While several included studies found associations between methylation levels and periodontal disease risk, there is insufficient evidence to support or refute an association between DNA methylation and periodontal disease/therapy in human adults. Further research must be conducted to identify reproducible epigenetic markers and determine the extent to which DNA methylation can be applied as a clinical biomarker.
Topics: Cyclooxygenase 2; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation; Genetic Markers; Histone Code; Histones; Humans; Interferon-gamma; Interleukin-6; Periodontal Diseases; Receptors, Interleukin-6; Suppressor of Cytokine Signaling 1 Protein; Tumor Necrosis Factor-alpha
PubMed: 32867386
DOI: 10.3390/ijms21176217 -
Epigenomics Jun 2022We systematically reviewed and evaluated current literature on alcohol consumption and DNA methylation (DNAm) at the genome-wide and probe-wise level in blood of... (Review)
Review
We systematically reviewed and evaluated current literature on alcohol consumption and DNA methylation (DNAm) at the genome-wide and probe-wise level in blood of adults. Five databases (PubMed, Embase, Web of Science, CINAHL and PsycInfo) were searched until 20 December 2020. Studies assessing the effect of alcohol dependence on DNAm were not eligible. 11 cross-sectional studies were included with 88 to 9643 participants. Overall, all studies had a risk of bias criteria unclear or unmet. Epigenome-wide association studies identified between 0 and 5458 differentially methylated positions, and 15 were observed in at least four studies. Potential methylation markers for alcohol consumption have been identified, but further validation in large cohorts is needed.
Topics: Adult; Alcohol Drinking; Alcoholism; Cross-Sectional Studies; DNA Methylation; Epigenesis, Genetic; Epigenome; Genome-Wide Association Study; Humans
PubMed: 35762294
DOI: 10.2217/epi-2022-0055 -
Environmental Pollution (Barking, Essex... Sep 2021This systematic review and meta-analysis aimed to investigate the association between air pollution and DNA methylation in adults from published observational studies.... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis aimed to investigate the association between air pollution and DNA methylation in adults from published observational studies. PubMed, Web of Science and Embase databases were systematically searched for available studies on the association between air pollution and DNA methylation published up to March 9, 2021. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS). Meta-analysis was used to summarize the combined estimates for the association between air pollutants and global DNA methylation levels. Heterogeneity was assessed with the Cochran Q test and quantified with the I statistic. In total, 38 articles were included in this study: 16 using global methylation, 18 using candidate genes, and 11 using EWAS, with 7 studies using more than one approach. Meta-analysis revealed an imprecise but inverse association between exposure to PM and global DNA methylation (for each 10-μg/m PM, combined estimate: 0.39; 95% confidence interval: 0.97 - 0.19). The candidate-gene results were consistent for the ERCC3 and SOX2 genes, suggesting hypermethylation in ERCC3 associated with benzene and that in SOX2 associated with PM exposure. EWAS identified 201 CpG sites and 148 differentially methylated regions that showed differential methylation associated with air pollution. Among the 307 genes investigated in 11 EWAS, a locus in nucleoredoxin gene was found to be positively associated with PM in two studies. Current meta-analysis indicates that PM is imprecisely and inversely associated with DNA methylation. The candidate-gene results consistently suggest hypermethylation in ERCC3 associated with benzene exposure and that in SOX2 associated with PM exposure. The Kyoto Encyclopedia of Genes and Genomes (KEGG) network analyses revealed that these genes were associated with African trypanosomiasis, Malaria, Antifolate resistance, Graft-versus-host disease, and so on. More evidence is needed to clarify the association between air pollution and DNA methylation.
Topics: Air Pollutants; Air Pollution; DNA Methylation; Environmental Exposure; Observational Studies as Topic; Particulate Matter
PubMed: 33895575
DOI: 10.1016/j.envpol.2021.117152 -
Clinical Epigenetics Sep 2023Undernutrition in pregnant women is an unfavorable environmental condition that can affect the intrauterine development via epigenetic mechanisms and thus have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Undernutrition in pregnant women is an unfavorable environmental condition that can affect the intrauterine development via epigenetic mechanisms and thus have long-lasting detrimental consequences for the mental health of the offspring later in life. One epigenetic mechanism that has been associated with mental disorders and undernutrition is alterations in DNA methylation. The effect of prenatal undernutrition on the mental health of adult offspring can be analyzed through quasi-experimental studies such as famine studies. The present systematic review and meta-analysis aims to analyze the association between prenatal famine exposure, DNA methylation, and mental disorders in adult offspring. We further investigate whether altered DNA methylation as a result of prenatal famine exposure is prospectively linked to mental disorders.
METHODS
We conducted a systematic search of the databases PubMed and PsycINFO to identify relevant records up to September 2022 on offspring whose mothers experienced famine directly before and/or during pregnancy, examining the impact of prenatal famine exposure on the offspring's DNA methylation and/or mental disorders or symptoms.
RESULTS
The systematic review showed that adults who were prenatally exposed to famine had an increased risk of schizophrenia and depression. Several studies reported an association between prenatal famine exposure and hyper- or hypomethylation of specific genes. The largest number of studies reported differences in DNA methylation of the IGF2 gene. Altered DNA methylation of the DUSP22 gene mediated the association between prenatal famine exposure and schizophrenia in adult offspring. Meta-analysis confirmed the increased risk of schizophrenia following prenatal famine exposure. For DNA methylation, meta-analysis was not suitable due to different microarrays/data processing approaches and/or unavailable data.
CONCLUSION
Prenatal famine exposure is associated with an increased risk of mental disorders and DNA methylation changes. The findings suggest that changes in DNA methylation of genes involved in neuronal, neuroendocrine, and immune processes may be a mechanism that promotes the development of mental disorders such as schizophrenia and depression in adult offspring. Such findings are crucial given that undernutrition has risen worldwide, increasing the risk of famine and thus also of negative effects on mental health.
Topics: Pregnancy; Adult; Female; Humans; DNA Methylation; Famine; Mental Disorders; Vitamins; Malnutrition
PubMed: 37716973
DOI: 10.1186/s13148-023-01557-y -
Atherosclerosis Aug 2017The aim of this study was to perform a systematic review of the association between DNA methylation and coronary heart disease (CHD) or related atherosclerotic traits. (Review)
Review
BACKGROUND AND AIMS
The aim of this study was to perform a systematic review of the association between DNA methylation and coronary heart disease (CHD) or related atherosclerotic traits.
METHODS
A systematic review was designed. The condition of interest was DNA methylation, and the outcome was CHD or other atherosclerosis-related traits. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS). A functional analysis was undertaken using the Ingenuity Pathway Analysis software.
RESULTS
In total, 51 articles were included in the analysis: 12 global methylation, 34 candidate-gene and 11 EWAS, with six studies using more than one approach. The results of the global methylation studies were inconsistent. The candidate-gene results were consistent for some genes, suggesting that hypermethylation in ESRα, ABCG1 and FOXP3 and hypomethylation in IL-6 were associated with CHD. The EWAS identified 84 genes showing differential methylation associated with CHD in more than one study. The probability of these findings was <1.37·10. One third of these genes have been related to obesity in genome-wide association studies. The functional analysis identified several diseases and functions related to these set of genes: inflammatory, metabolic and cardiovascular disease.
CONCLUSIONS
Global DNA methylation seems to be not associated with CHD. The evidence from candidate-gene studies was limited. The EWAS identified a set of 84 genes highlighting the relevance of obesity, inflammation, lipid and carbohydrate metabolism in CHD. This set of genes could be prioritized in future studies assessing the role of DNA methylation in CHD.
Topics: Atherosclerosis; Coronary Disease; DNA Methylation; Epigenesis, Genetic; Epigenomics; Gene Regulatory Networks; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Phenotype; Risk Factors; Signal Transduction
PubMed: 28577936
DOI: 10.1016/j.atherosclerosis.2017.05.022 -
Pharmacotherapy Apr 2020The pharmacoepigenetics of antipsychotic treatment in severe mental illness is a growing area of research that aims to understand the interface between antipsychotic...
The pharmacoepigenetics of antipsychotic treatment in severe mental illness is a growing area of research that aims to understand the interface between antipsychotic treatment and genetic regulation. Pharmacoepigenetics may some day assist in identifying treatment response mechanisms or become one of the components in the implementation of precision medicine. To understand the current evidence regarding the effects of antipsychotics on DNA methylation a systematic review with qualitative synthesis was performed through Pubmed, Embase and Psychinfo from earliest data to June 2019. Studies were included if they analyzed DNA methylation in an antipsychotic-treated population of patients with schizophrenia or bipolar disorder. Data extraction occurred via a standardized format and study quality was assessed. Twenty-nine studies were identified for inclusion. Study design, antipsychotic type, sample source, and methods of DNA methylation measurement varied across all studies. Eighteen studies analyzed methylation in patients with schizophrenia, four studies in patients with bipolar disorder, and seven studies in a combined sample of schizophrenia and bipolar disorder. Twenty-two studies used observational samples whereas the remainder used prospectively treated samples. Six studies assessed global methylation, five assessed epigenome-wide, and 15 performed a candidate epigenetic study. Two studies analyzed both global and gene-specific methylation, whereas one study performed a simultaneous epigenome-wide and gene-specific study. Only three genes were analyzed in more than one gene-specific study and the findings were discordant. The state of the pharmacoepigenetic literature on antipsychotic use is still in its early stages and uniform reporting of methylation site information is needed. Future work should concentrate on using prospective sampling with appropriate control groups and begin to replicate many of the novel associations that have been reported.
Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Schizophrenia
PubMed: 32058614
DOI: 10.1002/phar.2375 -
PloS One 2016Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as... (Review)
Review
IMPORTANCE
Epigenetic 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).
OBJECTIVE
To systematically review studies investigating epigenetic marks in AD or PD.
METHODS
Eleven 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.
RESULTS
Of 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.
CONCLUSION
Many 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.
Topics: Alzheimer Disease; Bias; Cross-Sectional Studies; DNA Methylation; Epigenesis, Genetic; Genome, Human; Histone Code; Histones; Humans; Inflammation; Neurodegenerative Diseases; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 27973581
DOI: 10.1371/journal.pone.0167201