Effects of early- and mid-life stress on DNA methylation of genes associated with subclinical cardiovascular disease and cognitive impairment: a systematic review

Abstract

BackgroundTraditional and novel risk factors cannot sufficiently explain the differential susceptibility to cardiovascular disease (CVD). Epigenetics may serve to partially explain this residual disparity, with life course stressors shown to modify methylation of genes implicated in various diseases. Subclinical CVD is often comorbid with cognitive impairment (CI), which warrants research into the identification of common genes for both conditions.MethodsWe conducted a systematic review of the existing literature to identify studies depicting the relationship between life course stressors, DNA methylation, subclinical CVD, and cognition.ResultsA total of 16 articles (8 human and 8 animal) were identified, with the earliest published in 2008. Four genes (COMT, NOS3, Igfl1, and Sod2) were analyzed by more than one study, but not in association with both CVD and CI. One gene (NR3C1) was associated with both outcomes, albeit not within the same study. There was some consistency among studies with markers used for subclinical CVD and cognition, but considerable variability in stress exposure (especially in human studies), cell type/tissue of interest, method for detection of DNA methylation, and risk factors. Racial and ethnic differences were not considered, but analysis of sex in one human study found statistically significant differentially methylated X-linked loci associated with attention and intelligence.ConclusionsThis review suggests the need for additional studies to implement more comprehensive and methodologically rigorous study designs that can better identify epigenetic biomarkers to differentiate individuals vulnerable to both subclinical CVD and associated CI.Electronic supplementary materialThe online version of this article (10.1186/s12881-019-0764-4) contains supplementary material, which is available to authorized users.

Understanding Health Inequalities Through the Lens of Social Epigenetics

“…Epigenetic mechanisms respond to exogenous exposures and alter gene expression without changing the underlying genetic sequence ( 18 ). Epigenetic changes are increasingly accepted as markers and potential mediators of differential aging and life expectancy ( 54 ), and they may represent one mechanism by which deleterious social and economic exposures alter immune function, increase systemic inflammation, and influence other markers of complex chronic disease in the context of documented health inequalities ( 43 , 128 , 139 ). There are three types of epigenetic mechanisms: ( a ) microRNAs, ( b ) histone modifications, and ( c ) cytosine-phosphate-guanine (CpG) methylation (also referred to as DNAm).…”

Associations of peripheral blood DNA methylation and estimated monocyte proportion differences during infancy with toddler attachment style

“…Finally, COMT is wellcharacterized for its role in catecholamine neurotransmitter release and regulation. Both SNP variation and DNAm within COMT have been associated with cognitive outcomes, especially in association with early life experience (Bruder et al, 2005;Malhotra et al, 2002;Ursini et al, 2011;Vidrascu et al, 2019;Walton et al, 2014). Though this study only examined blood DNAm, the high concordance and variability in brain at the majority of CpGs, especially within the prefrontal cortex (BA10), (Table 3; Supplemental Figure 4) and established relation of attachment and cognition, lend credence to these CpGs as potential precursor biomarkers of cognitive and synaptic advantages associated with future secure attachment development.…”

N6-Methyladenine in Eukaryotic DNA: Tissue Distribution, Early Embryo Development, and Neuronal Toxicity

“…Furthermore, the role of the conserved methyltransferase and demethylase in the folate cycle and DNA methylation warrants further biochemical investigation. Increasing evidence highlights that chronical stress, particularly in early life, could interfere and regulate the levels of DNA methylation, which, in turn, acts on the expression of certain genes ( Murgatroyd et al, 2009 ; Uchida et al, 2011 ; Vidrascu et al, 2019 ). Our results from animals exposed to α-HBCDD during early life are consistent with alterations in DNA methylation, with decreased levels of 6mA in the cerebellum, revealing the importance of this modification in the processes initiated by stress.…”