-
Cells Nov 2023There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past... (Review)
Review
There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past decade, the epigenetic regulation (DNA methylation, histone modification, and non-coding RNAs) of gene expression has been raised as a critical determinant of RV development, RV physiological function, and RV pathological dysfunction. We thus aimed to perform an up-to-date review of the literature, gathering knowledge on the epigenetic modifications associated with RV function/dysfunction. Therefore, we conducted a systematic review of studies assessing the contribution of epigenetic modifications to RV development and/or the progression of RV dysfunction regardless of the causal pathology. English literature published on PubMed, between the inception of the study and 1 January 2023, was evaluated. Two authors independently evaluated whether studies met eligibility criteria before study results were extracted. Amongst the 817 studies screened, 109 studies were included in this review, including 69 that used human samples (e.g., RV myocardium, blood). While 37 proposed an epigenetic-based therapeutic intervention to improve RV function, none involved a clinical trial and 70 are descriptive. Surprisingly, we observed a substantial discrepancy between studies investigating the expression (up or down) and/or the contribution of the same epigenetic modifications on RV function or development. This exhaustive review of the literature summarizes the relevant epigenetic studies focusing on RV in human or preclinical setting.
Topics: Humans; Heart Ventricles; Epigenesis, Genetic; Ventricular Dysfunction, Right; Myocardium; Ventricular Function, Right
PubMed: 38067121
DOI: 10.3390/cells12232693 -
Translational Psychiatry Feb 2021Childhood maltreatment is a major risk factor for chronic and severe mental and physical health problems across the lifespan. Increasing evidence supports the hypothesis... (Review)
Review
Childhood maltreatment is a major risk factor for chronic and severe mental and physical health problems across the lifespan. Increasing evidence supports the hypothesis that maltreatment is associated with epigenetic changes that may subsequently serve as mechanisms of disease. The current review uses a systematic approach to identify and summarize the literature related to childhood maltreatment and alterations in DNA methylation in humans. A total of 100 empirical articles were identified in our systematic review of research published prior to or during March 2020, including studies that focused on candidate genes and studies that leveraged epigenome-wide data in both children and adults. Themes arising from the literature, including consistent and inconsistent patterns of results, are presented. Several directions for future research, including important methodological considerations for future study design, are discussed. Taken together, the literature on childhood maltreatment and DNA methylation underscores the complexity of transactions between the environment and biology across development.
Topics: Adult; Child; Child Abuse; DNA Methylation; Epigenesis, Genetic; Epigenome; Humans; Risk Factors
PubMed: 33608499
DOI: 10.1038/s41398-021-01207-y -
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 Crohn's & Colitis Mar 2023Over the past decade, the DNA methylome has been increasingly studied in peripheral blood of inflammatory bowel disease [IBD] patients. However, a comprehensive summary... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Over the past decade, the DNA methylome has been increasingly studied in peripheral blood of inflammatory bowel disease [IBD] patients. However, a comprehensive summary and meta-analysis of peripheral blood leukocyte [PBL] DNA methylation studies has thus far not been conducted. Here, we systematically reviewed all available literature up to February 2022 and summarized the observations by means of meta-analysis.
METHODS
We conducted a systematic search and critical appraisal of IBD-associated DNA methylation studies in PBL using the biomarker-based cross-sectional studies [BIOCROSS] tool. Subsequently, we performed meta-analyses on the summary statistics obtained from epigenome-wide association studies [EWAS] that included patients with Crohn's disease [CD], ulcerative colitis [UC] and/or healthy controls [HC].
RESULTS
Altogether, we included 15 studies for systematic review. Critical appraisal revealed large methodological and outcome heterogeneity between studies. Summary statistics were obtained from four studies based on a cumulative 552 samples [177 CD, 132 UC and 243 HC]. Consistent differential methylation was identified for 256 differentially methylated probes [DMPs; Bonferroni-adjusted p ≤ 0.05] when comparing CD with HC and 103 when comparing UC with HC. Comparing IBD [CD + UC] with HC resulted in 224 DMPs. Importantly, several of the previously identified DMPs, such as VMP1/TMEM49/MIR21 and RPS6KA2, were consistently differentially methylated across all studies.
CONCLUSION
Methodological homogenization of IBD epigenetic studies is needed to allow for easier aggregation and independent validation. Nonetheless, we were able to confirm previous observations. Our results can serve as the basis for future IBD epigenetic biomarker research in PBL.
Topics: Humans; DNA Methylation; Cross-Sectional Studies; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Membrane Proteins
PubMed: 35998097
DOI: 10.1093/ecco-jcc/jjac119 -
Brain Sciences Mar 2023DNA methylation in genes of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with suicide behavior. Through a systematic review, we aimed to evaluate... (Review)
Review
DNA methylation in genes of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with suicide behavior. Through a systematic review, we aimed to evaluate DNA methylation levels of the genes involved in the HPA pathway and their association with suicide behavior. A search of articles was performed using PubMed and Science Direct, EBSCO. The terms included were "DNA methylation", "suicide", "epigenetics", "HPA axis" and "suicide behavior". This systematic review was performed by the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Six studies comprising 743 cases and 761 controls were included in this systematic review. The studies included individuals with suicide ideation, suicide attempts or completed suicide and childhood trauma, post-traumatic stress disorder (PTSD), or depression. One study reported hypermethylation in GR in childhood trauma, while two studies found hypermethylation of NR3C1 in childhood trauma and major depressive disorder (MDD). Only one study reported hypermethylation in BNDF in people with MDD. FKBP5 was found to be hypermethylated in people with MDD. Another study reported hypermethylation in CRHBP. SKA2 was reported to be hypermethylated in one study and another study found hypomethylated both in populations with PTSD. CRHR1 was found to be hypermethylated in people with MDD, and the last study found hypomethylation in CRH. Our result showed that patients with suicidal behavior showed a DNA methylation state of genes of the HPA axis in association with psychiatric comorbidity and with adverse events. Genes of the HPA axis could play a role in suicidal behavior associated with adverse events and pathologies. As a result, DNA methylation levels, proteins, and genes involved in the HPA axis could be considered for the search for biomarkers for the prevention of suicidal behavior in future studies.
PubMed: 37190549
DOI: 10.3390/brainsci13040584 -
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 -
Journal of Clinical Medicine Aug 2022: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate... (Review)
Review
: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. . To accomplish this, we collected all available data on methylation patterns in offspring conceived after ART and in spontaneously conceived (SC) offspring. We extracted 949 records. Of these, 50 were considered eligible; 12 were included in the quantitative synthesis. Methylation levels of CCCTC-binding factor 3 (CTCF3) were significantly lower in the ART group compared to controls (SMD -0.81 (-1.53; -0.09), I = 89%, = 0.03). In contrast, CCCTC-binding factor 6 (CTCF6), (), (), and () were not differently methylated in ART vs. SC offspring. : The methylation pattern of the offspring conceived after ART may be different compared to spontaneous conception. Due to the lack of studies and the heterogeneity of the data, further prospective and well-sized population studies are needed to evaluate the impact of ART on the epigenome of the offspring.
PubMed: 36078985
DOI: 10.3390/jcm11175056 -
Autoimmunity Jun 2022Sjögren's syndrome (SS) is a chronic systemic disease characterised by salivary and lacrimal gland dysfunction with severe implications for the well-being of bearing... (Review)
Review
Sjögren's syndrome (SS) is a chronic systemic disease characterised by salivary and lacrimal gland dysfunction with severe implications for the well-being of bearing individuals. Although its origin has not yet been fully elucidated, it is known that genetic, environmental, and epigenetic factors are important contributors to the pathogenesis of this syndrome. DNA methylation is a relevant, widely studied epigenetic factor that is possibly related to the establishment of SS. The aim of the present study was to perform a systematic review of the literature to compile studies on the contribution of DNA methylation to the pathogenesis of SS. A literature search was performed in 4 databases (PubMed, Web of Science, Lilacs, and Scopus) using previously selected Medical Subject Headings (MESH) descriptors, and article selection considered observational studies only. After a full-text reading of the selected articles, 15 studies were in accordance with the eligibility criteria for data extraction. Methylation detection approaches included global methylation, genome-wide assessment of differentially methylated regions, and site-specific methylation. Fourteen articles reported associations of DNA methylation profiles in SS patients, both globally and in several genes in salivary glands and blood cells. Thus, DNA methylation may contribute to the pathogenesis of SS. The findings reinforce the importance of epigenetic markers in the dynamics of SS and may direct efforts toward the development of new diagnostic and therapeutic approaches.
Topics: DNA Methylation; Humans; Salivary Glands; Sjogren's Syndrome
PubMed: 35403521
DOI: 10.1080/08916934.2022.2062593 -
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 -
International Journal of Surgery... Apr 2023Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early...
BACKGROUND
Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early detection and intervention can effectively improve the survival rate and quality of life. Although colonoscopy can detect and diagnose CRC, it is unsuitable for CRC screening in average-risk populations. Some commercial kits based on DNA mutation or methylation are approved for screening, but the low sensitivity for advanced adenoma or early-stage CRC would limit the applications.
MAIN RESULTS
Recently, researchers have focused on developing noninvasive or minimally invasive, easily accessible biomarkers with higher sensitivity and accuracy for CRC screening. Numerous reports describe advances in biomarkers, including DNA mutations and methylation, mRNA and miRNA, gut microbes, and metabolites, as well as low-throughput multiomics panels. In small cohorts, the specificity and sensitivity improved when fecal immunochemical testing combined with other biomarkers; further verification in large cohorts is expected. In addition, the continuous improvement of laboratory technology has also improved the sensitivity of detection technology, such as PCR, and the application of CRISPR/Cas technology. Besides, artificial intelligence has extensively promoted the mining of biomarkers. Machine learning was performed to construct a diagnosis model for CRC screening based on the cfDNA fragment features from whole-genome sequencing data. In another study, multiomics markers, including cfDNA, epigenetic, and protein signals, were also discovered by machine learning. Finally, advancements in sensor technology promote the applicability of volatile organic compounds in CRC early detection.
CONCLUSION
Here, the authors review advances in early detection and screening of CRC based on different biomarker types. Most studies reported optimistic findings based on preliminary research, and prospective clinical studies are ongoing. These promising biomarkers are expected to more accurately identify early-stage patients with CRC and be applied in the future.
Topics: Humans; Prospective Studies; Artificial Intelligence; Quality of Life; Biomarkers, Tumor; Early Detection of Cancer; DNA; Cell-Free Nucleic Acids; Colorectal Neoplasms
PubMed: 36974713
DOI: 10.1097/JS9.0000000000000260