Friso et al. (2008) |
Pro-spective |
HSD11β2 |
Methylation-specific PCR |
Peripheral blood (PBMC) |
Glucocorticoid treatment/hypertension |
N = 57 Italian subjects. 32 glucocorticoid-treated patients normotensive at baseline (mean age: 54.56 years; 4 men). 25 essential hypertensive patients (EH) (mean age: 51.92 years; 14 men) |
Glucocorticoid-treated patients who developed hypertension had:
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Greater HSD11β2 promoter methylation
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Higher urinary THFs/THE ratio, which indicates lower HSD11β2 protein activity
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Zhao et al. (2015) |
Cross-sectional |
NR3C1 |
Pyrosequencing |
Peripheral blood (leukocytes) |
Combat-related PTSD/Subclinical atherosclerosis |
N = 168 US veterans (84 monozygotic [MZ] twin pairs) (mean age: 55.1 years). The majority of twins were Caucasian (94%) and free of history of cardiovascular disease at enrollment |
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Except for LDL, there was no significant association between NR3C1 1F promoter methylation and standard coronary risk factors (e.g., triglycerides, blood pressure)
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Intra-pair difference in methylation was significantly and positively associated with intra-pair difference in flow-mediated dilation (FMD; determined using bi-mode ultrasound) at 50% (12/22) of studied CpG sites, and with mean DNA methylation across all studied CpG sites in the 1F promoter
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On average, 1% increase in the intra-pair difference in mean DNA methylation was associated with 2.83% increase in the intra-pair difference in FMD
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Methylation variation at each individual CpG site only conferred a small risk to disease, but the authors identified three methylation blocks (− 3365 to − 3371, − 3418 to − 3445, and − 3456 to − 3470 bp from ATG) that were significantly associated with FMD in their sample
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FMD-related methylation changes may therefore be systematically organized, rather than randomly distributed
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