Genomic 5-mC contents in peripheral blood leukocytes were independent protective factors for coronary artery disease with a specific profile in different leukocyte subtypes

Abstract

BackgroundAlterations in DNA methylation are demonstrated in atherosclerosis pathogenesis. However, changing rules of global DNA methylation and hydroxymethylation in peripheral blood leukocytes (PBLs) and different blood cell subtypes of coronary artery disease (CAD) patients are still inconclusive, and much less is known about mechanisms underlying.ResultsWe recruited 265 CAD patients and 270 healthy controls with genomic DNA from PBLs, of which 50 patients and 50 controls were randomly chosen with DNA from isolated neutrophils, lymphocytes and monocytes, and RNA from PBLs. Genomic 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) contents were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) assay. Genomic 5-mC contents were negatively associated with the serum total cholesterol (TC) level (P = 0.010), age (P = 0.016), and PBL classifications (P = 0.023), explaining 6.8% individual variation in controls. Furthermore, genomic 5-mC contents were inversely associated with an increased risk of CAD (odds ratio (OR) = 0.325, 95% confidence interval (CI) = 0.237~0.445, P = 2.62 × 10− 12), independent of PBL counts and classifications, age, sex, histories of hyperlipidemia, hypertension, and diabetes. Within-individual analysis showed a general 5-mC decrease in PBL subtypes, but significant difference was found in monocytes only (P = 0.001), accompanied by increased 5-hmC (P = 3.212 × 10− 4). In addition, coincident to the reduced DNMT1 expression in patients’ PBLs, the expression level of DNMT1 was significantly lower (P = 0.022) in oxidized low-density lipoprotein (ox-LDL) stimulated THP-1-derived foam cells compared to THP-1 monocytes, with decreased genomic 5-mdC content (P = 0.038).ConclusionsGlobal hypomethylation of blood cells defined dominantly by the monocyte DNA hypomethylation is independently associated with the risk of CAD in Chinese Han population. The importance of monocytes in atherosclerosis pathophysiology may demonstrate via an epigenetic pathway, but prospective studies are still needed to test the causality.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0443-x) contains supplementary material, which is available to authorized users.

Identification of potential biomarkers for CAD using integration with expression and methylation data and validation by case-control study

“…As the chromosome distribution map exhibited, differentially methylated CpGs covered almost every regions of each chromosome. This can be regarded as the universality of methylated regulation in the pathogenesis of CAD [24]. It is interesting to note that DMCs distributed in regions near centromeres were relatively fewer than other regions.…”

Folic acid modulates VPO1 DNA methylation levels and alleviates oxidative stress-induced apoptosis in vivo and in vitro

“…Thus, an unsuitable abundance of methyl groups due to an abnormal folate metabolism results in the depletion of SAM and an overall decrease in the methylation potential (the SAM: SAH ratio) [44] . Recently, Deng et al [45] found that global hypomethylation in blood cells, defined dominantly by monocyte DNA hypomethylation, is independently associated with the risk of coronary artery disease. Our previous studies [27] reported that folic acid upregulated the methylation potential in vivo and in vitro.…”

DNA methylation of noncoding RNAs: new insights into osteogenesis and common bone diseases

“…Epigenetic modifications, such as methylation and histone modifications, implicate in the heritable genetic changes without DNA sequence alteration often related to human disease [3]. DNA methylation is a kind of stable epigenetic modifications and refers to the addition of a methyl group (CH3) to the C-5 position of cytosine, which usually occurs in CpG islands [4]. CpG islands enrich cytosine and guanine sequences and account for 1% of the genome [5,6].…”