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Obesity Reviews : An Official Journal... Oct 2021Obesity is associated with widespread differential DNA methylation (DNAm) patterns, though there have been limited overlap in the obesity-associated cytosine-guanine... (Meta-Analysis)
Meta-Analysis Review
Obesity is associated with widespread differential DNA methylation (DNAm) patterns, though there have been limited overlap in the obesity-associated cytosine-guanine nucleotide pair (CpG) sites that have been identified in the literature. We systematically searched four databases for studies published until January 2020. Eligible studies included cross-sectional, longitudinal, or intervention studies examining adiposity and genome-wide DNAm in non-pregnant adults aged 18-75 in all tissue types. Study design and results were extracted in the descriptive review. Blood-based DNAm results in body mass index (BMI) and waist circumference (WC) were meta-analyzed using weighted sum of Z-score meta-analysis. Of the 10,548 studies identified, 46 studies were included in the systematic review with 18 and nine studies included in the meta-analysis of BMI and WC, respectively. In the blood, 77 and four CpG sites were significant in three or more studies of BMI and WC, respectively. Using a genome-wide threshold for significance, 52 blood-based CpG sites were significantly associated with BMI. These sites have previously been associated with many obesity-related diseases including type 2 diabetes, cardiovascular disease, Crohn's disease, and depression. Our study shows that DNAm at 52 CpG sites represent potential mediators of obesity-associated chronic diseases and may be novel intervention or therapeutic targets to protect against obesity-associated chronic diseases.
Topics: Adiposity; Adult; Body Mass Index; Cross-Sectional Studies; DNA Methylation; Diabetes Mellitus, Type 2; Humans; Obesity; Waist Circumference
PubMed: 34278703
DOI: 10.1111/obr.13319 -
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 -
Neuroscience and Biobehavioral Reviews May 2020DNA methylation (DNAm) - an epigenetic process that regulates gene expression - may represent a mechanism for the biological embedding of early traumatic experiences,...
DNA methylation (DNAm) - an epigenetic process that regulates gene expression - may represent a mechanism for the biological embedding of early traumatic experiences, including childhood maltreatment. Here, we conducted the first systematic review of human studies linking childhood maltreatment to DNAm. In total, 72 studies were included in the review (2008-2018). The majority of extant studies (i) were based on retrospective data in adults, (ii) employed a candidate gene approach (iii) focused on global maltreatment, (iv) were based on easily accessible peripheral tissues, typically blood; and (v) were cross-sectional. Two-thirds of studies (n = 48) also examined maltreatment-related outcomes, such as stress reactivity and psychiatric symptoms. While findings generally support an association between childhood maltreatment and altered patterns of DNAm, factors such as the lack of longitudinal data, low comparability across studies as well as potential genetic and 'pre-exposure' environmental confounding currently limit the conclusions that can be drawn. Key challenges are discussed and concrete recommendations for future research are provided to move the field forward.
Topics: Adult Survivors of Child Abuse; Adverse Childhood Experiences; DNA Methylation; Epigenesis, Genetic; Humans; Mental Disorders
PubMed: 32081689
DOI: 10.1016/j.neubiorev.2020.02.019 -
International Journal of Molecular... Oct 2022The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for... (Review)
Review
The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: , , , , , , and in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. , , , and genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing.
Topics: Biomarkers; Ceruloplasmin; Cross-Sectional Studies; DNA Methylation; Dyslipidemias; Gene Expression; Humans; Myeloid Differentiation Factor 88; Periodontitis; RNA
PubMed: 36233348
DOI: 10.3390/ijms231912042 -
BMC Pulmonary Medicine Mar 2017Epigenetic variations in peripheral blood have potential as biomarkers for disease. This systematic review assesses the association of lung function and chronic... (Review)
Review
BACKGROUND
Epigenetic variations in peripheral blood have potential as biomarkers for disease. This systematic review assesses the association of lung function and chronic obstructive pulmonary disease (COPD) with DNA methylation profiles in peripheral blood from population-based studies.
METHODS
Online databases Medline, Embase, and Web of Science were searched. Google Scholar was searched to identify grey literature. After removing duplicate articles, 1155 articles were independently screened by two investigators. Peer reviewed reports on population-based studies that examined peripheral blood DNA methylation in participants with measured lung function (FEV1, FEV1/FVC ratio) or known COPD status were selected for full-text review. Six articles were suitable for inclusion. Information regarding study characteristics, designs, methodologies and conclusions was extracted. A narrative synthesis was performed based on published results.
RESULTS
Three of the six articles assessed the association of COPD with DNA methylation, and two of these also included associations with lung function. Overall, five reports examined the association of lung function with DNA methylation profiles. Five of the six articles reported 'significant' results. However, no consistent CpG sites were identified across studies for COPD status or lung function values.
CONCLUSIONS
DNA methylation patterns in peripheral blood from individuals with reduced lung function or COPD may be different to those in people with normal lung function. However, this systematic review did not find any consistent associations of lung function or COPD with differentially methylated CpG sites. Large studies with a longitudinal design to address reverse causality may prove a more fruitful area of research.
TRIAL REGISTRATION
PROSPERO 2016: CRD42016037352 .
Topics: DNA Methylation; Epigenesis, Genetic; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests
PubMed: 28320365
DOI: 10.1186/s12890-017-0397-3 -
The interplay between DNA methylation and cardiac autonomic system functioning: a systematic review.International Journal of Environmental... Jan 2023Epigenetic marks, particularly DNA methylation (DNAm), are emerging as an important biological marker of susceptibility to cardiac autonomic dysfunction. This review... (Review)
Review
Epigenetic marks, particularly DNA methylation (DNAm), are emerging as an important biological marker of susceptibility to cardiac autonomic dysfunction. This review summarizes recent discoveries about the association between DNAm and cardiac autonomic activity. A systematic literature search was performed through the Embase, Web of Science, Cochrane Library, Pubmed, PsycINFO, and Pilots databases. Twenty-two studies met inclusion criteria, of which 18 were human studies including a total of 2,686 participants. DNAm differences in multiple genes, such as , and , linked environmental stressors to physiological responses. For instance, exposure to psychosocial stressors increased methylation, which was associated with both decreased blood pressure and increased parasympathetic activity. Additionally, played a potential role in cardiac autonomic dysfunction in an occupational setting, affecting the heart rate's deceleration capacity in welders. This review's findings suggest that DNAm is involved in cardiac autonomic regulation under different stress-mediated responses.
Topics: Humans; DNA Methylation; Autonomic Nervous System; Biomarkers
PubMed: 34753378
DOI: 10.1080/09603123.2021.2000590 -
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... Apr 2023This systematic review and meta-analysis summarize the difference in the methylation of the gene in patients with abnormal versus normal conventional sperm parameters.... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis summarize the difference in the methylation of the gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.
Topics: Female; Humans; Male; Pregnancy; DNA Methylation; Genomic Imprinting; Histones; Infertility, Male; Meta-Analysis as Topic; Semen; Spermatozoa
PubMed: 37108386
DOI: 10.3390/ijms24087224 -
International Journal of Molecular... Jan 2020Major depressive disorder (MDD) is the leading cause of disability worldwide and is associated with high rates of suicide and medical comorbidities. Current...
Major depressive disorder (MDD) is the leading cause of disability worldwide and is associated with high rates of suicide and medical comorbidities. Current antidepressant medications are suboptimal, as most MDD patients fail to achieve complete remission from symptoms. At present, clinicians are unable to predict which antidepressant is most effective for a particular patient, exposing patients to multiple medication trials and side effects. Since MDD's etiology includes interactions between genes and environment, the epigenome is of interest for predictive utility and treatment monitoring. Epigenetic mechanisms of antidepressant medications are incompletely understood. Differences in epigenetic profiles may impact treatment response. A systematic literature search yielded 24 studies reporting the interaction between antidepressants and eight genes (, , , , , ) and whole genome methylation. Methylation of certain sites within , , , , , and the whole genome was predictive of antidepressant response. Comparing DNA methylation in patients during depressive episodes, during treatment, in remission, and after antidepressant cessation would help clarify the influence of antidepressant medications on DNA methylation. Individuals' unique methylation profiles may be used clinically for personalization of antidepressant choice in the future.
Topics: Antidepressive Agents; DNA Methylation; Depressive Disorder, Major; Epigenesis, Genetic; Humans; Treatment Outcome
PubMed: 32012861
DOI: 10.3390/ijms21030826 -
Psychiatry Research Jan 2022Schizophrenia has a large disease burden globally. Early intervention in psychosis, and therefore a decreased duration of untreated psychosis, has a positive clinical... (Review)
Review
BACKGROUND
Schizophrenia has a large disease burden globally. Early intervention in psychosis, and therefore a decreased duration of untreated psychosis, has a positive clinical impact. There are several recognized risk factors for psychosis, including trauma history and substance use. This systematic review examined the literature for studies related to epigenetic changes in first-episode psychosis, with the goal of identifying future research directions.
METHODS
A literature review was conducted from inception to October 3, 2021 using MedLine/PubMed, Web of Science, and PsycInfo searches with the keywords ("first-episode schizophrenia" OR "first-episode psychosis" OR "drug-naive schizophrenia" OR "drug-naive psychosis") AND (epigenetic OR methylation OR hydroxymethylation OR "histone modification" OR "miRNA") as well as a search of the bibliography of the identified papers.
RESULTS
Seventeen studies that examined various portions of the genome were included in this systematic review. There were two studies that showed hypomethylation at the LINE-1 portion of the genome and two that showed hypermethylation at LINE-1. Additionally, two studies showed hypomethylation specifically at the GRIN2B promoter (part of LINE-1).
CONCLUSIONS
Although sample sizes were small, these studies provide evidence for epigenetic alterations in early psychosis. Further research in this area is warranted for more definitive epigenetic correlations.
Topics: DNA Methylation; Epigenesis, Genetic; Humans; Promoter Regions, Genetic; Psychotic Disorders; Schizophrenia
PubMed: 34896847
DOI: 10.1016/j.psychres.2021.114325