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Journal of Affective Disorders Jun 2019Child maltreatment predicts a significant risk factor for depression. The relationship between child maltreatment and depression has been shown to vary as a function of...
BACKGROUND
Child maltreatment predicts a significant risk factor for depression. The relationship between child maltreatment and depression has been shown to vary as a function of genetic factors. There have been very few systematic reviews conducted to date to synthesize what DNA methylations and/ or genetic variations interact with childhood maltreatment in the course of depression. This systematic review aimed to provide an overview of DNA methylation modifications with/without genetic variations associated with childhood maltreatment in depression.
METHODS
Computerized and manual search on six databases (EMBASE, HealthStar, PsychoInfo, Medline, PubMed and Cochrane Library) and grey literature up to June 30th 2018 were conducted. Studies were critically evaluated for their eligibility and study quality.
RESULTS
The initial search resulted in 196 articles. Five articles met the eligibility criteria being included in this review. All the selected studies were from the United States and published within the last five years. Changes in ID3, TPPP, GRIN1, and OXTR DNA methylation sites were found to be involved in the childhood maltreatment-depression relationship.
LIMITATIONS
The number of eligible articles included in this review was small. Selected articles had small sample sizes. A high degree of heterogeneity was found. It is difficult to conclude what the roles of DNA methylation modifications are in the relationship between maltreatment and depression. Population stratification has not been extensively studied so far and should be considered in the further research.
CONCLUSIONS
This review synthesizes an overview of the interaction between childhood maltreatment, DNA methylation modifications and genetic variations in depression. Findings of this review highlight an urgent need for genetic and epigenetic research in the area of childhood maltreatment and depression. Future etiological explorations should target on the above identified sites.
Topics: Adult; Adult Survivors of Child Abuse; Child; Child Abuse; DNA Methylation; Depressive Disorder; Female; Genetic Variation; Humans; Male; Risk Factors
PubMed: 30999089
DOI: 10.1016/j.jad.2019.04.049 -
Epigenomics Sep 2017Despite numerous published prognostic methylation markers for renal cell carcinoma (RCC), none of these have yet changed patient management. Our aim is to systematically... (Meta-Analysis)
Meta-Analysis Review
AIM
Despite numerous published prognostic methylation markers for renal cell carcinoma (RCC), none of these have yet changed patient management. Our aim is to systematically review and evaluate the literature on prognostic DNA methylation markers for RCC.
MATERIALS & METHODS
We conducted an exhaustive search of PubMed, EMBASE and MEDLINE up to April 2017 and identified 49 publications. Studies were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, assessed for their reporting quality using the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) criteria, and were graded to determine the level of evidence (LOE) for each biomarker.
RESULTS
We identified promoter methylation of BNC1, SCUBE3, GATA5, SFRP1, GREM1, RASSF1A, PCDH8, LAD1 and NEFH as promising prognostic markers. Extensive methodological heterogeneity across the included studies was observed, which hampers comparability and reproducibility of results, providing a possible explanation why these biomarkers do not reach the clinic.
CONCLUSION
Potential prognostic methylation markers for RCC have been identified, but they require further validation in prospective studies to determine their true clinical value.
Topics: Biomarkers, Tumor; Cadherins; Calcium-Binding Proteins; Carcinoma, Renal Cell; DNA Methylation; DNA-Binding Proteins; GATA5 Transcription Factor; Humans; Intercellular Signaling Peptides and Proteins; Kidney Neoplasms; Membrane Proteins; Neurofilament Proteins; Promoter Regions, Genetic; Protocadherins; Transcription Factors; Tumor Suppressor Proteins
PubMed: 28803494
DOI: 10.2217/epi-2017-0040 -
BMC Cancer Jan 2011The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with... (Meta-Analysis)
Meta-Analysis Review
O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction.
BACKGROUND
The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP.
METHODS
A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance.
RESULTS
Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value.
CONCLUSIONS
Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.
Topics: Brain Neoplasms; DNA Methylation; Humans; Immunohistochemistry; Neoplasms; O(6)-Methylguanine-DNA Methyltransferase; Polymerase Chain Reaction; Prognosis; Promoter Regions, Genetic
PubMed: 21269507
DOI: 10.1186/1471-2407-11-35 -
Neuroscience and Biobehavioral Reviews Apr 2023Epigenomic modifications of the brain-derived neurotrophic factor (BDNF) gene have been postulated to underlie the pathogenesis of neurodevelopmental, psychiatric, and... (Review)
Review
Epigenomic modifications of the brain-derived neurotrophic factor (BDNF) gene have been postulated to underlie the pathogenesis of neurodevelopmental, psychiatric, and neurological conditions. This systematic review summarizes current evidence investigating the association of BDNF epigenomic modifications (DNA methylation, non-coding RNA, histone modifications) with brain-related phenotypes in humans. A novel contribution is our creation of an open access web-based application, the BDNF DNA Methylation Map, to interactively visualize specific positions of CpG sites investigated across all studies for which relevant data were available. Our literature search of four databases through September 27, 2021 returned 1701 articles, of which 153 met inclusion criteria. Our review revealed exceptional heterogeneity in methodological approaches, hindering the identification of clear patterns of robust and/or replicated results. We summarize key findings and provide recommendations for future epigenomic research. The existing literature appears to remain in its infancy and requires additional rigorous research to fulfill its potential to explain BDNF-linked risk for brain-related conditions and improve our understanding of the molecular mechanisms underlying their pathogenesis.
Topics: Humans; Brain; Brain-Derived Neurotrophic Factor; DNA Methylation; Epigenomics; Phenotype
PubMed: 36764636
DOI: 10.1016/j.neubiorev.2023.105078 -
The Journals of Gerontology. Series A,... Feb 2020DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an individual's chronological age and can predict their risk of age-related disease and... (Meta-Analysis)
Meta-Analysis
DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an individual's chronological age and can predict their risk of age-related disease and mortality. This study reviewed the evidence that environmental, lifestyle and health factors are associated with the Horvath and Hannum epigenetic clocks. A systematic search identified 61 studies. Chronological age was correlated with DNAm age in blood (median .83, range .13-.99). In a meta-analysis body mass index (BMI) was associated with increased DNAm age (Hannum β: 0.07, 95% CI 0.04 to 0.10; Horvath β: 0.06, 95% CI 0.02 to 0.10), but there was no association with smoking (Hannum β: 0.12, 95% CI -0.50 to 0.73; Horvath β:0.18, 95% CI -0.10 to 0.46). DNAm age was positively associated with frailty (three studies, n = 3,093), and education was negatively associated with the Hannum estimate of DNAm age specifically (four studies, n = 13,955). For most other exposures, findings were too inconsistent to draw conclusions. In conclusion, BMI was positively associated with biological aging measured using DNAm, with some evidence that frailty also increased aging. More research is needed to provide conclusive evidence regarding other exposures. This field of research has the potential to provide further insights into how to promote slower biological aging and ultimately prolong healthy life.
Topics: Age Factors; Aging; Body Mass Index; DNA Methylation; Environment; Health Status; Humans; Life Style
PubMed: 31001624
DOI: 10.1093/gerona/glz099 -
Placenta Nov 2020Pre-eclampsia (PE) is the major cause of fetal and maternal mortality and can be classified according to gestational age of onset into early-onset (EOPE, <34 weeks of... (Meta-Analysis)
Meta-Analysis
Pre-eclampsia (PE) is the major cause of fetal and maternal mortality and can be classified according to gestational age of onset into early-onset (EOPE, <34 weeks of gestation) and late- (LOPE, ≥34 weeks of gestation). DNA methylation (DNAm) may help to understand the abnormal placentation in PE. Therefore, we performed a systematic review to assess the role of global DNAm on pathophysiology of PE, focused on fetal and maternal tissues of placenta from pregnant with PE, including EOPE and LOPE. We searched the databases EMBASE, Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus, Lilacs, Scielo and Google Scholar, and followed the MOOSE guidelines. Moreover, we performed pathway analysis with the overlapping genes from the included studies. Twelve out of 24 included studies in the qualitative analysis considered the classification into EOPE and LOPE. We did not found heterogeneity in the criteria used for diagnosis of PE, and a few studies evaluated whether confounding factors would influence placental DNAm. Fourteen out of 24 included studies showed hypomethylation in placental tissue from pregnant with PE compared to controls. The differences in DNAm are specific to genes or differentially methylated regions, and more evident in EOPE and preterm PE compared to controls, rather than LOPE and term PE. The overlapping genes from included studies revealed pathways relevant to pathophysiology of PE. Our findings highlighted the heterogeneous results of the included studies, mainly focused on North America and China. Replication studies in different populations should use the same placental tissues, techniques to assess DNAm and pipelines for bioinformatic analysis.
Topics: DNA Methylation; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy
PubMed: 32942147
DOI: 10.1016/j.placenta.2020.09.004 -
Obesity Reviews : An Official Journal... Jan 2022The tremendous increase in childhood obesity prevalence over the last few decades cannot merely be explained by genetics and evolutionary changes in the genome, implying...
The tremendous increase in childhood obesity prevalence over the last few decades cannot merely be explained by genetics and evolutionary changes in the genome, implying that gene-environment interactions, such as epigenetic modifications, likely play a major role. This systematic review aims to summarize the evidence of the association between epigenetics and childhood obesity. A literature search was performed via PubMed and Scopus engines using a combination of terms related to epigenetics and pediatric obesity. Articles studying the association between epigenetic mechanisms (including DNA methylation and hydroxymethylation, non-coding RNAs, and chromatin and histones modification) and obesity and/or overweight (or any related anthropometric parameters) in children (0-18 years) were included. The risk of bias was assessed with a modified Newcastle-Ottawa scale for non-randomized studies. One hundred twenty-one studies explored epigenetic changes related to childhood obesity. DNA methylation was the most widely investigated mechanism (N = 101 studies), followed by non-coding RNAs (N = 19 studies) with evidence suggestive of an association with childhood obesity for DNA methylation of specific genes and microRNAs (miRNAs). One study, focusing on histones modification, was identified. Heterogeneity of findings may have hindered more insights into the epigenetic changes related to childhood obesity. Gaps and challenges that future research should face are herein described.
Topics: Child; DNA Methylation; Epigenesis, Genetic; Histones; Humans; MicroRNAs; Pediatric Obesity; RNA, Untranslated
PubMed: 34816569
DOI: 10.1111/obr.13389 -
Public Health Genomics 2020The complex genetic diversity among human populations results from an assortment of factors acting at various sequential levels, including mutations, population...
SNPs in Sites for DNA Methylation, Transcription Factor Binding, and miRNA Targets Leading to Allele-Specific Gene Expression and Contributing to Complex Disease Risk: A Systematic Review.
INTRODUCTION
The complex genetic diversity among human populations results from an assortment of factors acting at various sequential levels, including mutations, population migrations, genetic drift, and selection. Although there are a plethora of DNA sequence variations identified through genome-wide association studies (GWAS), the challenge remains to explain the mechanisms underlying interindividual phenotypic disparity accounting for disease susceptibility. Single nucleotide polymorphisms (SNPs) present in the sites for DNA methylation, transcription factor (TF) binding, or miRNA targets can alter the gene expression. The systematic review aimed to evaluate the complex crosstalk among SNPs, miRNAs, DNA methylation, and TFs for complex multifactorial disease risk.
METHODS
PubMed and Scopus databases were used from inception until May 15, 2019. Initially, screening of articles involved studies assessing the interaction of SNPs with TFs, DNA methylation, or miRNAs resulting in allele-specific gene expression in complex multifactorial diseases. We also included the studies which provided experimental validation of the interaction of SNPs with each of these factors. The results from various studies on multifactorial diseases were assessed.
RESULTS
A total of 11 articles for SNPs interacting with DNA methylation, 30 articles for SNPs interacting with TFs, and 11 articles for SNPs in miRNA binding sites were selected. The interactions of SNPs with epigenetic factors were found to be implicated in different types of cancers, autoimmune diseases, cardiovascular diseases, diabetes, and asthma.
CONCLUSION
The systematic review provides evidence for the interplay between genetic and epigenetic risk factors through allele-specific gene expression in various complex multifactorial diseases.
Topics: Alleles; Binding Sites; DNA Methylation; Epigenesis, Genetic; Gene Expression; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; MicroRNAs; Phenotype; Polymorphism, Single Nucleotide; Risk Factors; Transcription Factors
PubMed: 32966991
DOI: 10.1159/000510253 -
Biomarkers : Biochemical Indicators of... May 2014An increasing number of methylated genes have been reported as biomarkers for the diagnosis of bladder cancer. However, the results have been inconsistent. We performed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An increasing number of methylated genes have been reported as biomarkers for the diagnosis of bladder cancer. However, the results have been inconsistent. We performed a systematic review and meta-analysis to evaluate the feasibility and accuracy of using methylated genes as diagnostic markers for bladder cancer risk.
METHODS
Studies were systemically searched via the PubMed, ProQuest Health & Medical Complete and Springer Link database up to September 2013. Studies reporting the sensitivity and specificity of methylated biomarkers were extracted and the diagnostic accuracies were assessed by pooled diagnostic odds ratios (DORs) with 95% confidence intervals (CIs).
RESULTS
Methylated biomarkers showed accuracy for detecting bladder cancer (urine samples: DOR = 36.48, 95% CI = 7.12-186.81; tissue samples: DOR = 68.71, 95% CI = 36.52-129.29). Summary receiver operating characteristic analysis showed that markers in urine had better diagnostic power than those in tissues (area under the curve: 0.89 versus 0.75).
CONCLUSION
The results of this study suggest that methylated biomarkers are suitable for diagnosing cancer risk.
Topics: Biomarkers, Tumor; DNA Methylation; Humans; Urinary Bladder Neoplasms
PubMed: 24693860
DOI: 10.3109/1354750X.2014.889211 -
Scientific Reports Jan 2018The relationship between O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and clinicopathological characteristics of non-small-cell lung carcinoma... (Meta-Analysis)
Meta-Analysis Review
The relationship between O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) has remained controversial and unclear. Therefore, in this study we have undertaken a systematic review and meta-analysis of relevant studies to quantitatively investigate this association. We identified 30 eligible studies investigating 2714 NSCLC patients. The relationship between MGMT hypermethylation and NSCLC was identified based on 20 studies, including 1539 NSCLC patient tissue and 1052 normal and adjacent tissue samples (OR = 4.60, 95% CI = 3.46~6.11, p < 0.00001). MGMT methylation varied with ethnicity (caucasian: OR = 4.56, 95% CI = 2.63~7.92, p < 0.00001; asian: OR = 5.18, 95% CI = 2.03~13.22, p = 0.0006) and control style (autologous: OR = 4.44, 95% CI = 3.32~5.92, p < 0.00001; heterogeneous: OR = 9.05, 95% CI = 1.79~45.71, p = 0.008). In addition, MGMT methylation was observed to be specifically associated with NSCLC clinical stage, and not with age, sex, smoking, pathological types, and differentiation status. Also MGMT methylation did not impact NSCLC patients survival (HR = 1.32, 95% CI = 0.77~2.28, p = 0.31). Our study provided clear evidence about the association of MGMT hypermethylation with increased risk of NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Genetic Association Studies; Humans; Lung Neoplasms; Male; Neoplasm Staging; Promoter Regions, Genetic; Tumor Suppressor Proteins
PubMed: 29362385
DOI: 10.1038/s41598-018-19949-z