Medical morbidities and DNA methylation of NR3C1 in preterm infants

Giarraputo, James; DeLoach, Jordan; Padbury, Jamés F.; Uzun, Alper; Marsit, Carmen J.; Hawes, Katheleen; Lester, Barry M.

doi:10.1038/pr.2016.185

Cited by 22 publications

(20 citation statements)

References 39 publications

(46 reference statements)

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“…Specifically, increased methylation of glucocorticoid receptor gene was observed in the first 4 days following preterm birth. However, findings remain inconsistent as studies demonstrated both decreased and increased DNA methylation of NR3C1 in high-risk preterm infants [i.e., scoring high on Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) or more medical problems] compared to low-risk preterm infants ( 200 , 201 ).…”

Section: Mechanisms Underlying Later Life Resilience and Vulnerabilitmentioning

confidence: 99%

Premature Birth and Developmental Programming: Mechanisms of Resilience and Vulnerability

et al. 2021

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The third trimester of pregnancy represents a sensitive phase for infant brain plasticity when a series of fast-developing cellular events (synaptogenesis, neuronal migration, and myelination) regulates the development of neural circuits. Throughout this dynamic period of growth and development, the human brain is susceptible to stress. Preterm infants are born with an immature brain and are, while admitted to the neonatal intensive care unit, precociously exposed to stressful procedures. Postnatal stress may contribute to altered programming of the brain, including key systems such as the hypothalamic–pituitary–adrenal axis and the autonomic nervous system. These neurobiological systems are promising markers for the etiology of several affective and social psychopathologies. As preterm birth interferes with early development of stress-regulatory systems, early interventions might strengthen resilience factors and might help reduce the detrimental effects of chronic stress exposure. Here we will review the impact of stress following premature birth on the programming of neurobiological systems and discuss possible stress-related neural circuits and pathways involved in resilience and vulnerability. Finally, we discuss opportunities for early intervention and future studies.

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Section: Mechanisms Underlying Later Life Resilience and Vulnerabilitmentioning

confidence: 99%

Premature Birth and Developmental Programming: Mechanisms of Resilience and Vulnerability

et al. 2021

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“…Several platforms for detecting aberrantly methylated DNA are available, such as Illumina HumanMethylation 450 BeadChip array, DREAMing, and Illumina HumanMethylation27 Bead-Chip [ 59 , 60 , 61 , 62 , 63 , 64 , 65 ], but only NGS reports accurate information regarding the methylation status of each cytosine of the DNA loci. In order to reveal the simultaneous methylation of two cytosines in one DNA loci in clinical diagnostics, next-generation MPS combined with target enrichment protocols [ 66 ] can be employed, as well as mass-spectrometry-based platforms, such as MassARRAY from Agena Bioscience Inc. Actually, the last platform allows the fast and cost-efficient visualization of cytosines in given positions and can be modified to perform simultaneous cytosine localizations.…”

Section: Discussionmentioning

confidence: 99%

Locus-Specific Methylation of GSTP1, RNF219, and KIAA1539 Genes with Single Molecule Resolution in Cell-Free DNA from Healthy Donors and Prostate Tumor Patients: Application in Diagnostics

Bryzgunova

Bondar

Ruzankin

et al. 2021

Cancers

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The locus-specific methylation of three genes (GSTP1, RNF219, and KIAA1539 (also known as FAM214B)) in the blood plasma cell-free DNA (cfDNA) of 20 patients with prostate cancer (PCa), 18 healthy donors (HDs), and 17 patients with benign prostatic hyperplasia (BPH) was studied via the MiSeq platform. The methylation status of two CpGs within the same loci were used as the diagnostic feature for discriminating the patient groups. Many variables had good diagnostic characteristics, e.g., each of the variables GSTP1.C3.C9, GSTP1.C9, and GSTP1.C9.T17 demonstrated an 80% sensitivity at a 100% specificity for PCa patients vs. the others comparison. The analysis of RNF219 gene loci methylation allowed discriminating BPH patients with absolute sensitivity and specificity. The data on the methylation of the genes GSTP1 and RNF219 allowed discriminating PCa patients, as well as HDs, with absolute sensitivity and specificity. Thus, the data on the locus-specific methylation of cfDNA (with single-molecule resolution) combined with a diagnostic approach considering the simultaneous methylation of several CpGs in one locus enabled the discrimination of HD, BPH, and PCa patients.

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“…Although tissue specificity of NR3C1 DNAm likely exists, both placental tissue and our target tissue, buccal epithelial cells (or saliva), may represent key developmental phenotypes and have utility as biomarkers (Armstrong et al, 2014). In a recent study of infant buccal epithelial cells, preterm infants with more medical morbidities had lower NR3C1 DNAm, and the authors speculated DNAm as potentially promoting adaptive programming (Giarraputo et al, 2017). Further, in a study of mothers with posttraumatic stress disorder (PTSD), lower NR3C1 DNAm in saliva was associated with greater symptom severity and parenting stress; the authors posited that NR3C1 DNAm effect direction could be dependent on how exposures are individually “processed,” reflecting the importance of context (Schechter et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Neonatal NR3C1 Methylation and Social-Emotional Development at 6 and 18 Months of Age

Folger

Ding

et al. 2019

Front. Behav. Neurosci.

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The variation in childhood social-emotional development within at-risk populations may be attributed in part to epigenetic mechanisms such as DNA methylation (DNAm) that respond to environmental stressors. These mechanisms may partially underlie the degree of vulnerability (and resilience) to negative social-emotional development within adverse psychosocial environments. Extensive research supports an association between maternal adversity and offspring DNAm of the NR3C1 gene, which encodes the glucocorticoid receptor (GR). A gap in knowledge remains regarding the relationship between NR3C1 DNAm, measured in neonatal (1-month of age) buccal cells, and subsequent social-emotional development during infancy and early childhood. We conducted a longitudinal cohort study of n = 53 mother-child dyads (n = 30 with developmental outcomes formed the basis of current study) who were enrolled in a home visiting (HV) program. Higher mean DNAm of the NR3C1 exon 1F promoter was significantly associated with lower 6-month Ages and Stages Questionnaire: Social-Emotional (ASQ:SE) scores—more positive infant social-emotional functioning. A similar trend was observed at 18-months of age in a smaller sample (n = 12). The findings of this pilot study indicate that in a diverse and disadvantaged population, the level of neonatal NR3C1 DNAm is related to later social-emotional development. Limitations and implications for future research are discussed.

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Medical morbidities and DNA methylation of NR3C1 in preterm infants

Cited by 22 publications

References 39 publications

Premature Birth and Developmental Programming: Mechanisms of Resilience and Vulnerability

Premature Birth and Developmental Programming: Mechanisms of Resilience and Vulnerability

Locus-Specific Methylation of GSTP1, RNF219, and KIAA1539 Genes with Single Molecule Resolution in Cell-Free DNA from Healthy Donors and Prostate Tumor Patients: Application in Diagnostics

Neonatal NR3C1 Methylation and Social-Emotional Development at 6 and 18 Months of Age

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