International Journal of Inflammation / 2019 / Article / Tab 3

Review Article

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

Table 3

Epigenome-wide and histone acetylation approaches and inflammatory markers.

AuthorStudy designOutcomeTissue typePopulation
Sex/Age/Sample size/ Country
Methylation sites/ methodAdjustmentMain findings

Epigenome-Wide Association Study

Guénard et al., 2013 [34]CSCRPWBM and W/12.25±5.77/ n=50/CanadaInfinium HumanMethylation 450K BeadChipAge and sexFrom 17 genes involved in the IL-8 signalling pathway, significant correlations between gene methylation and plasma CRP levels were found for 16 genes. Of these, 9 showed inverse correlation and 7 positive. Out of those 16 genes, 13 remained significant after adjustments.

Sun et al., 2013 [43]CSCPRPBLM and F/ 66.27±7.58/ n=966/ USAInfinium HumanMethylation 27K BeadChipAge, sex, BMI, smoking207 out of 257 CRP-associated DNAm sites showed an inverse correlation of greater methylation with lower level of CRP. Twenty-four out of the top 30 CpGs remained significant in both replication subsets with KLK10, LMO2 and TM4SF4 as top genes (p=5.85x10−12, p=1.69x10−11 and p=2.05x10−10, respectively).

Ligthart et al., 2016 [13]CSCRPWBM and W/mean age between 60 and 87/n=8,863/ ConsortiaIllumina Infinium HumanMethylation 27K and 450K BeadChip.Age, sex, white blood cell proportion, technical covariates, smoking, BMI.218 CpG sites were significantly associated with CRP. Of those, 125 CpGs were positively associated and 93 were negatively associated.
58 CpG sites, in 47 genes, were still significantly associated in the replication cohort (n=4,111). The top CpG sites were located in AIM, RPS6KA2 and PHOSPHO1 (P = 2.53x10−27, 2.06x10−26 and 4.87x10−25, respectively).

Marzi et al., 2016 [33]CSCRPPBM and W/60.9±8.89/ n=1741/ GermanyIllumina HumanMethylation 450K BeadChipAge, sex, BMI, smoking, white blood cells composition.Four CpG sites were significantly hypomethylated at high CRP concentrations. They were located at AQP3, BCL3, SOCS3, and intergenic at chromosome 19p13.2. Those four sites were replicated in three subcohorts: CpG at AQP3 remained significant in two of the subcohorts and the one at SOCS3 remained significant in one of the subcohorts.

Ahsan et al., 2017 [30]CS121 biomarkers related with inflammation, cancer, and cardiovascular disease.PBLM and W/ 14-97/ n=698/SwedenIllumina HumanMethylation 450K BeadChipAge, sex, batch and plate effects, year of sampling and cell fractions.For 36% of the studied biomarkers (44/121), the abundance level was associated with DNA methylation, but for 52% of these biomarkers (23/44), the associations were explained by genetic variants. For a subset of biomarkers, the association with DNA methylation was confounded by environmental factors (e.g., smoking), but for the majority of the associations, no such relationship could be found.

Verschoor et al., 2017 (“The relation between…”) [31]CSTNF, IL-6, IL-8, IL-10WBM and W/48-78/n=14/CanadaIllumina Infinium HumanMethylation 450 K BeadChipAge and sexSerum IL-10 levels exhibited the most substantial association to DNA methylation patterns, followed by TNF, IL-6 and IL-8.

Verschoor et al., 2017 (“DNA methylation…”) [32]CSTNF, IL-6, IL-1β, IL-10 and CRPPBMCM and W/82-98/n=23/CanadaIllumina Infinium HumanMethylation 450 K BeadChipAuthors performed linear regression between each factor assessed and the scores of top 10 principal components (PCs) of the DNA methylation dataset. Only IL-6 and IL-10 were found to be associated, both of which with PC7 (ln IL-6, p = 0.002; ln IL-10, p= 0.03). ln CRP was positively associated with DNA methylation age using Hannum's approach (β = 0.21, p = 0.007), which relates to approximately 5-years age acceleration per 1-unit change in ln CRP (β= 0.20, p =0.008).

Histone acetylation

da Silva et al., 2017 [15]CSIL-4, IL-6, IL-9, INF- γ and TGF-βPBMCM and W/ 68.5±6.49/n=10/ BrazilGlobal Histone H4 Acetylation Assay KitAt 24th session, the basal values of global histone H4 acetylation levels were correlated with basal IL-4 and IL-8 levels (r =−0.65, p= 0.04 and r=0.85, p=0.01, respectively).

CS: cross-sectional; WB: whole blood; M: men; W: women; IL: interleukin; PBL: peripheral blood leucocytes; BMI: body mass index; PB: peripheral blood; TNF: tumour necrosis factor; PBMC: peripheral blood mononuclear cells; INF-γ: interferon-gamma; TGF-β: transforming growth factor-beta.

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