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Table 1 Associations between DNA methylation and subclinical cardiovascular disease

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

  Lead Author, Publication Date Exposure Outcome Gene (s) with Greatest Association Regions Analyzed for Methylation Methylation Method Summary of Correlations
Human Studies Chen et al. 201639 Obstructive sleep apnea Hypertensions ASF1A, KLHL28*, CCL26, CNR1, CTSZ, CXCR3, FLJ46358, GIMAP5, HOXB2, IL1R2, LTA, TMEM175*, OFD1, OR10H2, OR1G1, ORM1, PTCD2, SP140, TRHR, TRPM2, PRSS1*, NRSN1* Promoter regions analyzed in 22 genes HumanMethylation27 Bead Chip and Pyrosequencing Both ↑ and ↓ methylation in 22 genes associated with ↑ hypertension
Kheirandish-Gozal et al. 201338 Obstructive sleep apnea Endothelial dysfunction (post occlusive hyperemic response) NOS3** Proximal promoter region analyzed Pyrosequencing ↑ methylation at CpG site (− 171 bp from TSS) correlated with ↑ endothelial dysfunction
Nanayakkara et al. 200826 Stage 2–4 chronic kidney disease Atherosclerosis (CCA-IMT) Endothelial dysfunction (BA-FMD) Genome-wide Liquid chromatography-tandem mass spectrometry (LC-MS/MS) No correlation between methylation and either atherosclerosis or endothelial dysfunction
Zhao et al. 201537 Vietnam war veteran Endothelial dysfunction (BA-FMD) NR3C1 22 CpG sites analyzed within exon 1F promoter region Pyrosequencing ↑ methylation at 12 CpG residues associated with ↑ endothelial dysfunction
Animal Studies Chu et al. 201544 Intermittent hypoxia Endothelial dysfunction (post ischemic reperfusion response) Hypertension (systolic blood pressure) Ace***, Agt CpG island surrounding TSS of Ace gene analyzed Regulatory region 3000 bp upstream of TSS of Agt gene analyzed DNA methylation-sensitive enzymatic restriction and quantitative PCR Trend towards ↓ methylation at a CpG island in Ace TSS and upstream of Agt TSS in association with ↑ endothelial dysfunction and ↑ hypertension
Nanduri et al. 201243 Intermittent hypoxia Cardio-respiratory dysfunction (breathing, blood pressure) Sod2 Bisulfite sequencing ↑ methylation at a CpG site in the first intron (+ 128 bp from TSS) associated with ↑ cardio-respiratory dysfunction
Nanduri et al. 201740 Intermittent hypoxia Hypertension (blood pressure) Prdx4, Sod1, Sod2, Txnrd2 Bisulfite sequencing and Epitect Methyl II custom PCR array ↑ methylation in 3 genes and at CpG region 4 (+ 157 bp from TSS) of Sod2 associated with ↑ blood pressure
Yang et al. 201541 Normobaric hypoxia Pulmonary hypertension (RVSP, PVR, RVH) Igfl1 CpG sites around promoter region analyzed Amplicon sequencing ↑ methylation at 1 out of 5 CpG sites around promoter region associated with ↑ pulmonary hypertension; ↑ global DNA methylation after 2 weeks of chronic hypoxia
Zhang et al. 201442 Extrauterine growth restriction Pulmonary hypertension (RVSP, RVH, PVR, PAP) Nos3**, Fgfr2, Igfl1, Med1****, Rhoc, Notch1 DML withinpromoter region and CpG islands analyzed MeDIP-chip microarray ↑ methylation within promoter of Fgfr2, Rhoc, Notch1, and Igf1 associated with development of hypertension; no difference in total methylation within Nos3 and Med1 promoter regions
  1. sself-report
  2. *reported as BTBD5, MGC4618, TRY1, and VMP, respectively, in Chen et al. 2016 study; **reported as eNOS in Kheirandish-Gozal et al. 2013 and Zhang et al. 2014 studies; ***reported as Ace1 in Chu et al. 2015 study; ****reported as Ppar in Zhang et al. 2014 study
  3. Note: complete list of identified genes is not included for study Chen et al. 2016
  4. CVD cardiovascular disease; BA-FMD brachial artery flow-mediated dilatation; CCA-IMT common carotid artery intima-media thickness; NA non-applicable; PAP pulmonary artery pressure; PVR pulmonary vascular remodeling, RVH right ventricular hypertrophy; RVSP right ventricular systolic pressure; TSS transcription start site