Table 1 Associations between DNA methylation and subclinical cardiovascular disease
| Â | 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 |