Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans

Antiplatelet therapy has become a cornerstone in the treatment of coronary heart disease (CHD). However, due to high-residual-platelet-reactivity, clopidogrel resistance (CR) is a common phenomenon, and it is rarely known about the relationship between CR and epigenetic changes. This study compared the whole genomic methylation patterns of blood samples from patients with CR (n = 6) and non-CR (n = 6) with the Human Methylation 850K BeadChip assay. We explored differentially methylated CpG sites, genes, and pathways using bioinformatics profiling. The CR and control groups showed significantly different DNA methylation at 7,098 sites, with 979 sites showing hypermethylation and 6,119 sites showing hypomethylation. The pyrosequencing method was used to validate four differentially methylated CpG loci (cg23371584, cg15971518, cg04481923, cg22507406), confirming that DNA methylation was associated with the risk of CR (30 CR vs. 30 non-CR). The relative mRNA expression of the four genes (BTG2, PRG2, VTRNA2-1, PER3) corresponding to the loci above was also associated with CR, suggesting that alterations in DNA methylation may affect the expression of these four genes, eventually resulting in CR. Additionally, differentially methylated sites are partially related to genes and pathways that play key roles in process of circadian entrainment, insulin secretion, and so on. Hence, the mechanism and biological regulation of CR might be reflected through these epigenetic alterations, but future research will need to address the causal relationships.

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Epigenetic Age Acceleration and Hearing: Observations From the Baltimore Longitudinal Study of Aging

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.790926 ◽

2021 ◽

Vol 13 ◽

Author(s):

Pei-Lun Kuo ◽

Ann Zenobia Moore ◽

Frank R. Lin ◽

Luigi Ferrucci

Keyword(s):

Dna Methylation ◽

Longitudinal Study ◽

Smoking History ◽

Future Research ◽

Age Related ◽

Epigenetic Age ◽

Epigenetic Age Acceleration ◽

Baltimore Longitudinal Study ◽

Age Related Hearing Loss ◽

The Relationship

Objectives: Age-related hearing loss (ARHL) is highly prevalent among older adults, but the potential mechanisms and predictive markers for ARHL are lacking. Epigenetic age acceleration has been shown to be predictive of many age-associated diseases and mortality. However, the association between epigenetic age acceleration and hearing remains unknown. Our study aims to investigate the relationship between epigenetic age acceleration and audiometric hearing in the Baltimore Longitudinal Study of Aging (BLSA).Methods: Participants with both DNA methylation and audiometric hearing measurements were included. The main independent variables are epigenetic age acceleration measures, including intrinsic epigenetic age acceleration—“IEAA,” Hannum age acceleration—“AgeAccelerationResidualHannum,” PhenoAge acceleration—“AgeAccelPheno,” GrimAge acceleration—“AgeAccelGrim,” and methylation-based pace of aging estimation—“DunedinPoAm.” The main dependent variable is speech-frequency pure tone average. Linear regression was used to assess the association between epigenetic age acceleration and hearing.Results: Among the 236 participants (52.5% female), after adjusting for age, sex, race, time difference between measurements, cardiovascular factors, and smoking history, the effect sizes were 0.11 995% CI: (–0.00, 0.23), p = 0.054] for Hannum’s clock, 0.08 [95% CI: (–0.03, 0.19), p = 0.143] for Horvath’s clock, 0.10 [95% CI: (–0.01, 0.21), p = 0.089] for PhenoAge, 0.20 [95% CI: (0.06, 0.33), p = 0.004] for GrimAge, and 0.21 [95% CI: (0.09, 0.33), p = 0.001] for DunedinPoAm.Discussion: The present study suggests that some epigenetic age acceleration measurements are associated with hearing. Future research is needed to study the potential subclinical cardiovascular causes of hearing and to investigate the longitudinal relationship between DNA methylation and hearing.

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Parenting stress and DNA methylation among African Americans in the InterGEN Study

Journal of Clinical and Translational Science ◽

10.1017/cts.2018.3 ◽

2017 ◽

Vol 1 (6) ◽

pp. 328-333 ◽

Cited By ~ 11

Author(s):

Michelle L. Wright ◽

Yunfeng Huang ◽

Qin Hui ◽

Kevin Newhall ◽

Cindy Crusto ◽

...

Keyword(s):

Dna Methylation ◽

Parenting Stress ◽

Mixed Models ◽

Life Stress ◽

Significant Variation ◽

African Ancestry ◽

Maternal Parenting ◽

Maternal Parenting Stress ◽

Methylation Patterns ◽

The Relationship

IntroductionGeneral life stress has been associated with altered DNA methylation in individuals of African Ancestry, although the relationship between parenting stress and DNA methylation has not been described. The purpose of this study was to examine the relationship between maternal parenting stress and DNA methylation among African Ancestry mother-child dyads.MethodsWe evaluated epigenome-wide DNA methylation relative to parenting stress in 74 mother-child dyads using linear mixed models.ResultsSignificant variation in maternal DNA methylation at 95 CpG sites was associated with level of parenting stress. Notably, we identified a change in DNA methylation associated with poly (ADP-ribose) polymerase-1, which plays a key role in stress signaling. We did not identify any significant variation in child DNA methylation related to maternal parenting stress.ConclusionsHowever, DNA methylation patterns observed in children mirrored patterns observed in their mothers. The results suggest that differential maternal DNA methylation is associated with higher levels of parenting stress.

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Abstract 288: DNA methylation patterns in peripheral blood and the relationship with cancer susceptibility loci at chromosome 8q24

10.1158/1538-7445.am2014-288 ◽

2014 ◽

Author(s):

Kathryn Hughes Barry ◽

Lee Moore ◽

Joshua Sampson ◽

Liying Yan ◽

Ann Meyer ◽

...

Keyword(s):

Dna Methylation ◽

Peripheral Blood ◽

Cancer Susceptibility ◽

Susceptibility Loci ◽

Methylation Patterns ◽

The Relationship ◽

Chromosome 8Q24

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The Effects of Maternal and Postnatal Dietary Methyl Nutrients on Epigenetic Changes that Lead to Non-Communicable Diseases in Adulthood

International Journal of Molecular Sciences ◽

10.3390/ijms21093290 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3290 ◽

Cited By ~ 1

Author(s):

Raniru S. Randunu ◽

Robert F. Bertolo

Keyword(s):

Dna Methylation ◽

Metabolic Pathways ◽

Dietary Intervention ◽

Infant Nutrition ◽

Communicable Diseases ◽

Epigenetic Alterations ◽

Non Communicable Diseases ◽

Nutrient Manipulation ◽

Methylation Patterns ◽

Epigenetic Patterns

The risk for non-communicable diseases in adulthood can be programmed by early nutrition. This programming is mediated by changes in expression of key genes in various metabolic pathways during development, which persist into adulthood. These developmental modifications of genes are due to epigenetic alterations in DNA methylation patterns. Recent studies have demonstrated that DNA methylation can be affected by maternal or early postnatal diets. Because methyl groups for methylation reactions come from methionine cycle nutrients (i.e., methionine, choline, betaine, folate), deficiency or supplementation of these methyl nutrients can directly change epigenetic regulation of genes permanently. Although many studies have described the early programming of adult diseases by maternal and infant nutrition, this review discusses studies that have associated early dietary methyl nutrient manipulation with direct effects on epigenetic patterns that could lead to chronic diseases in adulthood. The maternal supply of methyl nutrients during gestation and lactation can alter epigenetics, but programming effects vary depending on the timing of dietary intervention, the type of methyl nutrient manipulated, and the tissue responsible for the phenotype. Moreover, the postnatal manipulation of methyl nutrients can program epigenetics, but more research is needed on whether this approach can rescue maternally programmed offspring.

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STEM-27. miR-10b-5p MODULATES 5hmC EXPRESSION AND THE STEM-LIKE PHENOTYPE IN GBM

Neuro-Oncology ◽

10.1093/neuonc/noaa215.844 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii202-ii202

Author(s):

Harmon Khela ◽

Sweta Sudhir ◽

Maria Lugo-Fagundo ◽

Bachchu Lal ◽

Hernando Lopez-Bertoni ◽

...

Keyword(s):

Dna Methylation ◽

Stem Cell Markers ◽

Tumor Initiation ◽

Epigenetic Alterations ◽

Sox2 Expression ◽

Initiation And Propagation ◽

Xenograft Models ◽

Non Coding Rnas ◽

Methylation Patterns ◽

Sphere Formation

Abstract Epigenetic alterations such as DNA methylation and dysregulation of non-coding RNAs (e.g. miRNAs) are found in all types of cancer and are thought to play important roles in tumorigenesis. GBM is characterized by small subsets of cells, referred to as glioma stem cells (GSCs), that display stem-like properties implicated in tumor initiation, therapeutic resistance, and recurrence. DNA methylation patterns are altered in GBM and GSCs and are thought to play critical roles in tumor initiation and propagation. DNA methylation is a reversible process catalyzed, in part, by the ten-eleven translocation (TET) family of enzymes. These enzymes function as deoxygenases that catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Multiple studies found negative correlations between 5hmC levels and glioma grade and loss of 5hmC correlates with poor prognosis of GBM patients. However, the mechanisms leading to the loss of 5hmC in glioma and the role this phenomenon plays in gliomagenesis remains poorly understood. We found that Sox2 expression decreases TET2 expression and its product 5hmC in GSCs and identified miR-10b-5p as a molecular intermediary of this process. We show that miR-10b-5p expression is high in GBM compared to non-tumor in clinical specimens and high levels of this miRNA correlate with poor patient outcome. Expression of transgenic miR-10b-5p enhanced sphere formation capacity of GSCs and the expression of stem cell markers and drivers. Additionally, using a combination of molecular and biochemical endpoints, we show that miR-10b-5p modifies 5hmC levels by regulating TET2 in GSCs. Finally, we show that repression of miR-10b-5p increases 5hmC levels and inhibits tumor propagation in GBM xenograft models. Taken together, these results present a new molecular mechanism that controls 5hmC and the tumor propagating capacity of GSCs and suggests that miR-10b-5p inhibition and other strategies for enhancing TET2 function can be developed to treat GBM.

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Establishment and Maintenance of Genomic Methylation Patterns in Mouse Embryonic Stem Cells by Dnmt3a and Dnmt3b

Molecular and Cellular Biology ◽

10.1128/mcb.23.16.5594-5605.2003 ◽

2003 ◽

Vol 23 (16) ◽

pp. 5594-5605 ◽

Cited By ~ 473

Author(s):

Taiping Chen ◽

Yoshihide Ueda ◽

Jonathan E. Dodge ◽

Zhenjuan Wang ◽

En Li

Keyword(s):

Dna Methylation ◽

De Novo ◽

Es Cells ◽

Embryonic Stem ◽

Single Copy ◽

Dna Methyltransferases ◽

Methylation Patterns ◽

Genomic Methylation ◽

De Novo Methylation

ABSTRACT We have previously shown that the DNA methyltransferases Dnmt3a and Dnmt3b carry out de novo methylation of the mouse genome during early postimplantation development and of maternally imprinted genes in the oocyte. In the present study, we demonstrate that Dnmt3a and Dnmt3b are also essential for the stable inheritance, or “maintenance,” of DNA methylation patterns. Inactivation of both Dnmt3a and Dnmt3b in embryonic stem (ES) cells results in progressive loss of methylation in various repeats and single-copy genes. Interestingly, introduction of the Dnmt3a, Dnmt3a2, and Dnmt3b1 isoforms back into highly demethylated mutant ES cells restores genomic methylation patterns; these isoforms appear to have both common and distinct DNA targets, but they all fail to restore the maternal methylation imprints. In contrast, overexpression of Dnmt1 and Dnmt3b3 failed to restore DNA methylation patterns due to their inability to catalyze de novo methylation in vivo. We also show that hypermethylation of genomic DNA by Dnmt3a and Dnmt3b is necessary for ES cells to form teratomas in nude mice. These results indicate that genomic methylation patterns are determined partly through differential expression of different Dnmt3a and Dnmt3b isoforms.

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Analysis of DNA Methylation Patterns Associated with In Vitro Propagated Globe Artichoke Plants Using an EpiRADseq-Based Approach

Genes ◽

10.3390/genes10040263 ◽

2019 ◽

Vol 10 (4) ◽

pp. 263 ◽

Cited By ~ 2

Author(s):

Elisa Cerruti ◽

Cinzia Comino ◽

Alberto Acquadro ◽

Gianpiero Marconi ◽

Anna Maria Repetto ◽

...

Keyword(s):

Dna Methylation ◽

Methylation Status ◽

Transcriptional Analysis ◽

Globe Artichoke ◽

Epigenetic Alterations ◽

Coding Regions ◽

Methylation Patterns ◽

Reproductive Processes ◽

Photosynthesis Regulation

Globe artichoke represents one of the main horticultural species of the Mediterranean basin, and ‘Spinoso sardo’ is the most widespread and economically relevant varietal type in Sardinia, Italy. In the last decades, in vitro culture of meristematic apices has increased the frequency of aberrant plants in open-field production. These off-type phenotypes showed highly pinnate-parted leaves and late inflorescence budding, and emerged from some branches of the true-to-type ‘Spinoso sardo’ plants. This phenomenon cannot be foreseen and is reversible through generations, suggesting the occurrence of epigenetic alterations. Here, we report an exploratory study on DNA methylation patterns in off-type/true-to-type globe artichoke plants, using a modified EpiRADseq technology, which allowed the identification of 2,897 differentially methylated loci (DML): 1,998 in CG, 458 in CHH, and 441 in CHG methylation contexts of which 720, 88, and 152, respectively, were in coding regions. Most of them appeared involved in primary metabolic processes, mostly linked to photosynthesis, regulation of flower development, and regulation of reproductive processes, coherently with the observed phenotype. Differences in the methylation status of some candidate genes were integrated with transcriptional analysis to test whether these two regulation levels might interplay in the emergence and spread of the ‘Spinoso sardo’ non-conventional phenotype.

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The effect of internal factors and family influence on firms’ adoption of green product innovation

Management Research Review ◽

10.1108/mrr-02-2015-0031 ◽

2016 ◽

Vol 39 (10) ◽

pp. 1167-1198 ◽

Cited By ~ 12

Author(s):

Yi-Chun Huang ◽

Min-Li Yang ◽

Ying-Jiuan Wong

Keyword(s):

Firm Size ◽

Family Firms ◽

Behavioral Theory ◽

Family Influence ◽

Future Research ◽

Green Product ◽

Internal Factors ◽

Content Type ◽

And Control ◽

The Relationship

Purpose Little research has been conducted on the internal factors that drive green product (GP) innovation and how family influence affects firm adoption of GP innovation. This study aims to apply multiple perspectives to bridge this research gap, adopting the resource-based view (RBV) to examine what and how internal factors affect firm adoption of GP innovation, and using the behavioral theory of family firms to investigate whether family influence fosters or hinders firm adoption of GP innovation. Design/methodology/approach This study used a multichannel approach and adopted content analysis to collect and evaluate data on listed Taiwanese firms and used cross-sectional regression analysis to examine the effect of internal factors and family influence on firm adoption of GP innovation. Findings The results showed that the internal factors of green capabilities, R&D intensity and firm size significantly and positively affected firm adoption of GP innovation separately. Furthermore, the study found that family influence (ownership and control) significantly and negatively affects firm adoption of GP innovation separately. Research limitations/implications This study contributes to the academic research of innovation management, green management and family firms in several aspects, but also has some limitations. This study examined only the relationship between a firm’s internal factors and GP innovation. Future research might test the relationship between a firm’s internal factors and adoption of green process innovation. In addition, such research can explore how integrated internal and external factors influence firm adoption of GP innovation. Practical implications From the RBV, the internal factors of green capabilities, R&D intensity and firm size that can exert crucial effects on firm engage in firm’s adoption of GP innovation. This study suggests that top managers in family-influenced businesses should maintain appropriate commitment and support for fostering and facilitating firm GP innovation. Social implications From the RBV, this study examined how internal factors affect firm adoption of GP innovation. Moreover, based on the behavioral theory of family firms, this study further examined how family influence (ownership and control) affects firm adoption of GP innovation. This paper extended both perspectives to examine green issues. Originality/value From the RBV, this study examined how internal factors affect firms’ GP innovation. Moreover, based on institutional theory, this study further examines how a family firm moderates the relationship between a firm’s internal factors and GP innovation. The paper extended both perspectives to probe further the green issues.

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Stress of Conscience among psychiatric nursing staff in relation to environmental and individual factors

Nursing Ethics ◽

10.1177/0969733011419239 ◽

2012 ◽

Vol 19 (2) ◽

pp. 208-219 ◽

Cited By ~ 23

Author(s):

Hanna Tuvesson ◽

Mona Eklund ◽

Christine Wann-Hansson

Keyword(s):

Aggressive Behavior ◽

Nursing Staff ◽

Perceived Control ◽

Future Research ◽

Individual Factors ◽

Psychosocial Work ◽

Ward Atmosphere ◽

Stress Of Conscience ◽

And Control ◽

The Relationship

The present study aimed at investigating the relationship between environmental and individual factors and Stress of Conscience among nursing staff in psychiatric in-patient care. A questionnaire involving six different instruments measuring Stress of Conscience, the ward atmosphere, the psychosocial work environment, Perceived Stress, Moral Sensitivity, and Mastery was answered by 93 nursing staff at 12 psychiatric in-patient wards in Sweden. The findings showed that Sense of Moral Burden, Mastery, Control at Work and Angry and Aggressive Behavior were related to Stress of Conscience. We conclude that Mastery and Control at Work seemed to work as protective factors, while Sense of Moral Burden and perceptions of Angry and Aggressive Behavior made the nursing staff more vulnerable to Stress of Conscience. Future research should investigate whether measures to increase the level of perceived control and being part of decision making will decrease the level of Stress of Conscience among the staff.

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