Epigenetics and Inflammatory Markers: A Systematic Review of the Current Evidence

Epigenetic mechanisms have been suggested to play a role in the genetic regulation of pathways related to infammation. Terefore, we aimed to systematically review studies investigating the association between DNA methylation and histone modifcations with circulatory infammation markers in blood. Five bibliographic databases were screened until 21 November of 2017. We included studies conducted on humans that examined the association between epigenetic marks (DNA methylation and/or histone modifcations) and a comprehensive list of infammatory markers. Of the 3,759 identifed references, 24 articles were included, involving, 17,399 individuals. Tere was suggestive evidence for global hypomethylation but better-quality studies in the future have to confrm this. Epigenome-wide association studies (EWAS) (n=7) reported most of the identifed diferentially methylated genes to be hypomethylated in infammatory processes. Candidate genes studies reported 18 diferentially methylated genes related to several circulatoryinfammation markers.Tere was no overlap in the methylated sites investigated in candidate gene studies and EWAS, except for TMEM49, which was found to be hypomethylated with higher infammatory markers in both types of studies. Te relation between histone modifcations and infammatory markers was assessed by one study only. Tis review supports an association between epigenetic marks and infammation, suggesting hypomethylation of the genome. Important gaps in the quality of studies were reported such as inadequate sample size, lack of adjustment for relevant confounders, and failure to replicate the fndings. While most of the studies have been focused on C-reactive protein, further eforts should investigate other infammatory markers.

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